Markers and cellular anteceents of rheumatoid arthritis flares

ABSTRACT

The present invention provides biological markers which are molecular and cellular antecedents of rheumatoid arthritis (RA) flares. The invention provides RNA and protein markers that can predict an RA flare one or two weeks prior to the flare. The invention further provides blood circulating cells, particularly pre-inflammatory mesenchymal cells, which are cellular precursors and indicators of an impending RA flare. The present invention further provides methods, kits and markers for identification and monitoring of flares in RA patients and their application as markers and targets in and for treatment of rheumatoid arthritis and conditions induced or related to rheumatoid arthritis.

STATEMENT OF GOVERNMENT RIGHTS

This invention was made with government support under numbers NS034389, NS081706, NS097404 and 1UM1HG008901 awarded by the National Institutes of Health. The government has certain rights in the invention.

FIELD OF THE INVENTION

The present invention relates generally to the identification and characterization of biological markers which are molecular antecedents of rheumatoid arthritis (RA) flares. The invention further relates to RNA and protein markers that can predict an RA flare one or two weeks prior to the flare. The invention further relates to blood circulating cells, particularly pre-inflammatory mesenchymal cells, which are cellular precursors and indicators of an impending RA flare. The present invention relates to methods, kits and markers for the identification and monitoring of flares in RA patients and their application as markers and targets in and for treatment of rheumatoid arthritis and conditions induced or related to rheumatoid arthritis.

BACKGROUND OF THE INVENTION

Rheumatoid arthritis (RA) is a chronic inflammatory disorder and is the most common form of autoimmune arthritis, affecting more than 1.3 million Americans. About 75% of RA patients are women and between 1 and 3% of women may get rheumiatoid arthritis in their lifetime. RA is a chronic disease affecting the lining of joints that causes joint pain, stiffness, swelling and decreased movement of the joints and can eventually result in bone erosion and joint deformity.

Treatments for RA can stop joint pain and swelling and prevent joint damage. Early treatment will give better long term results and patients receiving early treatment are less likely to have the type of joint damage that leads to joint replacement. The main treatment goals with rheumatoid arthritis are to control inflammation, relieve pain, and reduce disability associated with RA. Treatment usually includes medications, occupational or physical therapy, and regular exercise, although some patients ultimately need surgery, including synovectomy, tendon repair, joint fusion or total joint replacement to correct joint damage. Nonsteroidal anti-inflammatory drugs (NSAIDs) provide ‘first-line’ RA medicines to relieve pain and reduce inflammation. NSAIDs include non-prescription drugs acetylsalicylate (aspirin), ibuprofen (Advil, Motrin IB) and naproxen sodium (Aleve, Naprosyn) and prescription NSAIDs such as etodolac (Lodine) and diclofenac (Voltaren). Steroids are are anti-inflammatory or immunosuppressants agents and are prescribed for more severe RA or when RA symptoms flare to ease joint pain and stiffness. Examples of recognized steroids include glucocotricosteroids or corticosteroids such as prednisone, cortisone and methylprednisolone. Disease-modifying antirheumatic drugs (DMARDs) are prescribed and utilized to slow the progression of RA and save joints and other tissues from permanent damage. Common DMARDs include methotrexate (Trexall, Otrexup), leflunomide (Arava), hydroxychloroquine (Plaquenil) and sulfasalazine (Azulfidine). DMARDs curb the overactive immune system in RA but aren't selective in their targets. Side effects vary but may include liver damage, bone marrow suppression and severe lung infections. Biologics—genetically engineered proteins which target a specific aspect or part of the immune system and act as immunosuppressants—are an increasingly important component in treatment of RA. Tumor necrosis factor (TNF) inhibitors and non-TNF inhibitors (such as cytoking inhibitors, T or B cell inhibitors) are included among the recognizedbiologics for RA. Biologics include abatacept (Orencia), adalimumab (Humira), anakinra (Kineret), baricitinib (Olumiant), certolizumab (Cimzia), etanercept (Enbrel), golimumab (Simponi), infliximab (Remicade), rituximab (Rituxan), sarilumab (Kevzara), tocilizumab (Actemra) and tofacitinib (Xeljanz). Adalimumab, etanercept, infliximab, golimumab and certolizumab target TNF (Lis K et al (2014) Arch Med Sci 10(6):1175-1185). Rituximab depletes B cells. Anakinra blocks the action of interleukin-1 (IL-1), a master cytokine. Abatacept targets T cells. These types of drugs also increase the risk of infections. Biologic DMARDs are usually most effective when paired with a nonbiologic DMARD, such as methotrexate. New drugs which are specific in their targets but are not biologics include oral small molecule Janus kinase (JAK) inhibitors such as tofacitinib (Xeljanz and Xeljanz XR), baricitinib (Olumiant), and upadacitinib (Rinvoq). The antimetabolite Methotrexate is also often used to treat RA, including in combination with other DMARD drugs including biologic DMARDs.

Results from recent patient surveys report that three-fourths of RA patients are not satisfied with treatments and patients continued to experience bothersome symptoms that impacted their daily activities and life (Radawaski C et al (2019) Rheumatol Ther 6(3):461-471). RA, like many inflammatory diseases, is characterized by episodes of quiescence and exacerbation (flares). Flares are severe episodes of symptoms and reflect increased disease activity during which joint pain, swelling, and stiffness are more severe. The duration and intensity of flares vary, the flares are unpredictable, and the molecular events leading to flares are unknown. Such waxing/waning clinical courses are characteristic of many autoimmune diseases, including multiple sclerosis (MS) (Steinman L. (2014) Annu Rev Immunol 32:257-81), systemic lupus erythematosus (SLE) (Fava A, Petri M. (2019) J Autoimmun 96:1-13), and inflammatory bowel disease (IBD) (Braun J, Wei B (2007) Annu Rev Pathol 2:401-29; Braun J et al (2007) Arthritis Rheum 57:639-47.).

Like with RA, each and all of these common autoimmune diseases would be more appropriately managed and effectively treated if the clinical course could be more effectively evaluated and flares and disease exacerbations could be predicted or identified and treatment or therapeutic intervention could be initiated sooner and with better short and long-term results. There is need to develop approaches to understand what triggers transitions from quiescence to flare in autoimmune disease. There remains a need for improved disease management among currently treated RA and other auto-immune disease patients. The present invention addresses such unmet needs in the field and particularly with regard to rheumatoid arthritis (RA).

The citation of references herein shall not be construed as an admission that such is prior art to the present invention.

SUMMARY OF THE INVENTION

In a general aspect, the present invention provides antecedents of an RA flare. RNA markers and protein markers have been identified which are differentially expressed or preferentially expressed prior to an RA flare in an RA patient(s). These RNA transcripts provide markers which can predict an impending flare and the determination and presence of which can be utilized to implement and prescribe treatment and therapy to a patient(s).

The invention provides a method for monitoring and predicting a rheumatoid arthritis (RA) flare or increased RA disease activity in a patient comprising:

(a) isolating a blood sample from said patient;

(b) evaluating the blood sample for expression or quantitatively increased amounts of one or more sets of antecedent RNA markers, protein markers or cell markers selected from:

-   -   (i) AC2 markers or proteins as provided in Table 7;     -   (ii) AC3 markers or proteins as provided in Table 8;     -   (iii) markers or proteins selected from COL1A2, COL5A1, COL16A1,         COL14A1, COL4A2, PXDN, ST5, DCLK1, SCARA5, EGFR, EGR1, ZFHX4,         COL3A1, COMP, FNDC1, GALNT15, SULF1, GPX8 and IGFBP6 as set out         in Table 5;     -   (iv) markers or proteins selected from COL1A2, COL5A1, COL16A1,         COL14A1, COL4A2, PXDN, ST5, DCLK1, SCARA5, EGFR, EGR1 and ZFHX4         as set out in Table 9;     -   (v) cell markers CD45− CD31−PDPN+;

(c) wherein the expression or quantitatively increased amounts of the RNA markers or proteins or the presence of the cell markers predicts an impending RA flare.

The invention provides a method for monitoring and predicting a rheumatoid arthritis (RA) flare or increased RA disease activity in a patient comprising:

(a) isolating a blood sample from said patient;

(b) evaluating the blood sample for expression or quantitatively increased amounts of one or more sets of antecedent RNA markers, protein markers or cell markers selected from:

-   -   (i) markers or proteins selected from COL1A2, COL5A1, COL16A1,         COL14A1, COL4A2, PXDN, ST5, DCLK1, SCARA5, EGFR, EGR1, ZFHX4,         COL3A1, COMP, FNDC1, GALNT15, SULF1, GPX8 and IGFBP6 as set out         in Table 5;     -   (ii) markers or proteins selected from COL1A2, COL5A1, COL16A1,         COL14A1, COL4A2, PXDN, ST5, DCLK1, SCARA5, EGFR, EGR1 and ZFHX4         as set out in Table 9; (iii) AC2 markers or proteins as provided         in Table 7;     -   (iv) AC3 markers or proteins as provided in Table 8; and     -   (v) cell markers CD45− CD31−PDPN+;

(c) wherein the expression or quantitatively increased amounts of the RNA markers or proteins or the presence of the cell markers predicts an impending RA flare.

In an embodiment of the method, the expression or quantitatively increased amounts of the AC2 RNA markers or proteins predicts an RA flare in about 2 weeks or about 12-14 days. In an embodiment of the method, the expression or quantitatively increased amounts of the AC2 RNA markers or proteins predicts an RA flare in about 2 weeks, with a margin of error of about a week or further 7 days, thus in 7-21 days, or in up or about three weeks, up to 21 days or so.

In an embodiment of the method, the expression or quantitatively increased amounts of the AC3 RNA markers or proteins predicts an RA flare in about 1 week or about 5-7 days. In an embodiment of the method, the expression or quantitatively increased amounts of the AC3 RNA markers or proteins predicts an RA flare in about 1 week, with a margin of error of about a week or further 7 days, thus in 0-14 days, or in up or about two weeks, up to 14 days or so.

In an embodiment of the method, a subset of at least 20 of the AC2 or AC3 markers are evaluated. In an embodiment, a subset of at least 10 of the AC2 or AC3 markers are evaluated. At least 4, at least 5, at least 6, at least 7, at least 8, at least 9, at least 10, at least 11, at least 12, at least 13, at least 14, least 15, at least 16, at least 17, at least 18, at least 19, at least 20, at least 25, at least 30, at least 35, at least 40, at least 45, at least 50 of the AC2 or AC3 markers may evaluated.

In an embodiment of the method, a subset of at least 20 of the AC2 and and at least 20 of the AC3 markers are evaluated. In an embodiment, a subset of at least 10 of the AC2 and the AC3 markers are evaluated. At least 4, at least 5, at least 6, at least 7, at least 8, at least 9, at least 10, at least 11, at least 12, at least 13, at least 14, least 15, at least 16, at least 17, at least 18, at least 19, at least 20, at least 25, at least 30, at least 35, at least 40, at least 45, at least 50 of the AC2 and the AC3 markers may evaluated.

In an embodiment, sublining fibroblast markers selected from the AC3 markers or proteins are evaluated. In an embodiment, AC3 markers or proteins expressed by CD34+, HLADR+ and DKK3+ cells are evaluated. In an embodiment, AC3 markers or proteins expressed by CD45−, CD34+, HLADR+ and DKK3+ cells are evaluated.

The method includes, wherein the cell marker IL17RD is also evaluated.

The invention further provides a method(s) wherein the antecedent RNA markers or protein markers or selected from:

(a) AC3 markers or proteins as provided in Table 8;

(b) markers or proteins selected from COL1A2, COL5A1, COL16A1, COL14A1, COL4A2, PXDN, ST5, DCLK1, SCARA5, EGFR, EGR1, ZFHX4, COL3A1, COMP, FNDC1, GALNT15, SULF1, GPX8 and IGFBP6 as set out in Table 5; and

(c) markers or proteins selected from COL1A2, COL5A1, COL16A1, COL14A1, COL4A2, PXDN, ST5, DCLK1, SCARA5, EGFR, EGR1 and ZFHX4 as set out in Table 9; are reduced, significantly decreased, nearly absent, or absent in peripheral blood during an RA flare or once a patient exhibits symptoms of an RA flare.

The invention further provides a method(s) wherein the antecedent RNA markers or protein markers or selected from:

(a) markers or proteins selected from COL1A2, COL5A1, COL16A1, COL14A1, COL4A2, PXDN, ST5, DCLK1, SCARA5, EGFR, EGR1, ZFHX4, COL3A1, COMP, FNDC1, GALNT15, SULF1, GPX8 and IGFBP6 as set out in Table 5;

(b) markers or proteins selected from COL1A2, COL5A1, COL16A1, COL14A1, COL4A2, PXDN, ST5, DCLK1, SCARA5, EGFR, EGR1 and ZFHX4 as set out in Table 9; and

(c) AC3 markers or proteins as provided in Table 8; are reduced, significantly decreased, nearly absent, or absent in peripheral blood during an RA flare or once a patient exhibits symptoms of an RA flare.

The invention provides a method for predicting an impending RA flare and treating a flare in a patient, the method comprising:

a) isolating a blood sample from the patient;

b) contacting the blood sample with reagents specific for markers selected from a panel of RNA or protein markers to assess expression of the RNA or protein markers, wherein the panel of RNA or protein markers is selected from:

-   -   (i) AC2 markers or proteins as provided in Table 7;     -   (ii) AC3 markers or proteins as provided in Table 8;     -   (iii) markers or proteins selected from COL1A2, COL5A1, COL16A1,         COL14A1, COL4A2, PXDN, ST5, DCLK1, SCARA5, EGFR, EGR1, ZFHX4,         COL3A1, COMP, FNDC1, GALNT15, SULF1, GPX8 and IGFBP6 as set out         in Table 5; and     -   (iv) markers or proteins selected from COL1A2, COL5A1, COL16A1,         COL14A1, COL4A2, PXDN, ST5, DCLK1, SCARA5, EGFR, EGR1 and ZFHX4         as set out in Table 9;

c) comparing expression of the markers selected from a panel of RNA or protein markers in the blood sample to expression of the markers in a control blood sample to determine if expression of the markers selected from a panel of RNA or protein markers in the blood sample is increased relative to expression in the control blood sample, wherein detection of increased expression serves to predict an impending RA flare in a patient;

and treating the patient thereby diagnosed with an impending RA flare by administering a therapeutically effective amount of one or more disease modifying agent for treating RA.

The invention provides a method for predicting an impending RA flare and treating a flare in a patient, the method comprising:

a) isolating a blood sample from the patient;

b) contacting the blood sample with reagents specific for markers selected from a panel of RNA or protein markers to assess expression of the RNA or protein markers, wherein the panel of RNA or protein markers is selected from:

-   -   (i) markers or proteins selected from COL1A2, COL5A1, COL16A1,         COL14A1, COL4A2, PXDN, ST5, DCLK1, SCARA5, EGFR, EGR1, ZFHX4,         COL3A1, COMP, FNDC1, GALNT15, SULF1, GPX8 and IGFBP6 as set out         in Table 5;     -   (ii) markers or proteins selected from COL1A2, COL5A1, COL16A1,         COL14A1, COL4A2, PXDN, ST5, DCLK1, SCARA5, EGFR, EGR1 and ZFHX4         as set out in Table 9;     -   (iii) AC2 markers or proteins as provided in Table 7; and     -   (iv) AC3 markers or proteins as provided in Table 8;

c) comparing expression of the markers selected from a panel of RNA or protein markers in the blood sample to expression of the markers in a control blood sample to determine if expression of the markers selected from a panel of RNA or protein markers in the blood sample is increased relative to expression in the control blood sample, wherein detection of increased expression serves to predict an impending RA flare in a patient;

and treating the patient thereby diagnosed with an impending RA flare by administering a therapeutically effective amount of one or more disease modifying agent for treating RA.

In an embodiment of the method, the expression, differential expression, or quantitatively increased amounts of the AC2 RNA markers or proteins predicts an RA flare in about 2 weeks, about 14 days, or about 12-14 days.

In an embodiment of the method, the expression or quantitatively increased amounts of the AC3 RNA markers or proteins predicts an RA flare in about one week, about 7 days, or about 5-7 days. In an embodiment of the method, the expression, differential expression, or quantitatively increased amounts of the markers or proteins selected from COL1A2, COL5A1, COL16A1, COL14A1, COL4A2, PXDN, ST5, DCLK1, SCARA5, EGFR, EGR1, ZFHX4, COL3A1, COMP, FNDC1, GALNT15, SULF1, GPX8 and IGFBP6 or of the markers or proteins selected from COL1A2, COL5A1, COL16A1, COL14A1, COL4A2, PXDN, ST5, DCLK1, SCARA5, EGFR, EGR1 and ZFHX4 predicts an RA flare in about one week, about 7 days, or about 5-7 days.

In an embodiment of the method, the expression or quantitatively increased amounts of RNA or protein markers selected from:

(a) the AC3 RNA markers or proteins;

(b) markers or proteins selected from COL1A2, COL5A1, COL16A1, COL14A1, COL4A2, PXDN, ST5, DCLK1, SCARA5, EGFR, EGR1, ZFHX4, COL3A1, COMP, FNDC1, GALNT15, SULF1, GPX8 and IGFBP6; and

(c) markers or proteins selected from COL1A2, COL5A1, COL16A1, COL14A1, COL4A2, PXDN, ST5, DCLK1, SCARA5, EGFR, EGR1 and ZFHX4;

predicts an RA flare in about 1 week or about 5-7 days.

In an embodiment of the method, the expression or quantitatively increased amounts of RNA or protein markers selected from:

(a) markers or proteins selected from COL1A2, COL5A1, COL16A1, COL14A1, COL4A2, PXDN, ST5, DCLK1, SCARA5, EGFR, EGR1, ZFHX4, COL3A1, COMP, FNDC1, GALNT15, SULF1, GPX8 and IGFBP6;

(b) markers or proteins selected from COL1A2, COL5A1, COL16A1, COL14A1, COL4A2, PXDN, ST5, DCLK1, SCARA5, EGFR, EGR1 and ZFHX4; and

(c) the AC3 RNA markers or proteins;

predicts an RA flare in about 1 week or about 5-7 days.

Evaluation of RNA or protein expression may be evaluated or assessed using any method known in the art. Thus, in accordance with the methods of the invention, RNA expression may be assessed by RT PCR. In accordance with the method, protein expression may be assessed using specific antibodies.

Cell marker expression or presence on the surface of cells in the blood in accordance with the methods of the invention may be determined using standard and known methods. Cell markers may be evaluated using antibodies. Cell markers may be evaluated using Fluorescent Activated Cell Sorting (FACs) analysis. Cells or cell markers may be evaluated using cell sorting or single cell assessments.

In embodiments of the method of the invention, the disease modifying agent for treating RA may be selected from standard or clinically recognized agents or therapies for RA or arthritic conditions or inflammatory diseases and conditions. In embodiments of the method of the invention, the disease modifying agent for treating RA may be one or more agent selected from a nonsteroidal anti-inflammatory drug (NSAID), steroid, methotrexate, disease-modifying antirheumatic drug (DMARDs), biologic DMARD, and oral janus kinase (JAK) inhibitor. In an embodiment, the DMARD is selected from methotrexate (Trexall, Otrexup), leflunomide (Arava), hydroxychloroquine (Plaquenil) and sulfasalazine (Azulfidine). There are a variety of known biologic DMARD agents, including various agents being evaluated or with application to RA and/or other arthritic and/or inflammatory conditions.

In an aspect, the biologic DMARD may selected from abatacept (Orencia), adalimumab (Humira), anakinra (Kineret), baricitinib (Olumiant), certolizumab (Cimzia), etanercept (Enbrel), golimumab (Simponi), infliximab (Remicade), rituximab (Rituxan), sarilumab (Kevzara), tocilizumab (Actemra) and tofacitinib (Xeljanz). The biologic DMARD may be a tumor necrosis factor (TNF) inhibitor. In an aspect, the biologic DMARD may be an anti-inflammatory antibody or an antibody directed to an inflammation or immune modulatory molecule. In an aspect, the antibody may be an interleukin antibody. The antibody may be an IL-17 specific antibody or an IL-17RD specific or IL-17RD blocking or neutralizing antibody.

In an embodiment, the biologic DMARD is combined with an NSAID and/or with methotrexate. In an embodiment, the JAK inhibitor is selected from tofacitinib (Xeljanz and Xeljanz XR), baricitinib (Olumiant), and upadacitinib (Rinvoq).

The invention provides and relates to a circulating pre-inflammatory mesenchymal (PRIME) cell characterized as a CD45−CD31−PDPN+ cell, wherein the presence of the cell in peripheral blood is indicative or predictive of an impending RA flare. In an embodiment, the PRIME cell additionally expresses IL17RD and is IL17RD+. In an embodiment, a subset of PRIME cells additionally expresses IL17RD and is IL17RD+.

The invention further provides a method of predicting an impending RA flare comprising evaluating a blood sample from a patient for the presence of a PRIME cell characterized as a CD45−CD31−PDPN+ cell, wherein the presence of detectable PRIME cells in peripheral blood in a patient predicts an impending RA flare in the patient. In an embodiment thereof, the method includes further evaluating for the presence of IL17RD on a CD45−CD31−PDPN+ cell.

Methods are provided for evaluating and treating an impending flare in an RA patient comprising evaluating the peripheral blood of a patient for the presence of a PRIME cell characterized as a CD45−CD31−PDPN+ cell and treating a patient that is positive for PRIME cells in their peripheral blood with a disease modifying agent for RA. Methods are provided for evaluating and treating an impending flare in an RA patient comprising evaluating the peripheral blood of a patient for the presence of a PRIME cell characterized as a CD45−CD31−PDPN+IL17RD+ cell and treating a patient that is positive for PRIME cells in their peripheral blood with a disease modifying agent for RA.

In an additional embodiment of the method, the patient is treated with an IL-17 or IL-17RD antibody. In another embodiment, the patient is further treated with an anti-inflammatory agent and/or an immune modulating agent.

Methods are provided for evaluating and treating an impending flare in an RA patient comprising evaluating the peripheral blood of a patient for the presence of RNA(s) or protein(s) expressed, specifically expressed or particularly expressed by a PRIME cell characterized as a CD45− CD31−PDPN+ cell and treating a patient that is positive for expressing, specifically expressing or particularly expressing RNA(s) or protein(s) of PRIME cells in their peripheral blood with a disease modifying agent for RA. Methods are provided for evaluating and treating an impending flare in an RA patient comprising evaluating the peripheral blood of a patient for the presence of RNA(s) or protein(s) expressed, specifically expressed or particularly expressed by a cell characterized as a CD45−CD31−PDPN+IL17RD+ cell and treating a patient that is positive for the presence of RNA(s) or protein(s) expressed, specifically expressed or particularly expressed by a cell characterized as a CD45−CD31−PDPN+IL17RD+ cell in their peripheral blood with a disease modifying agent for RA.

The invention includes a set of RNA or protein markers for evaluating and predicting an impending RA flare in a patient comprising the markers selected from:

(i) a subset of at least 20 markers from the AC2 markers provided in Table 7;

(ii) a subset of at least 20 markers from the AC3 markers provided in Table 8;

(iii) markers selected from COL1A2, COL5A1, COL16A1, COL14A1, COL4A2, PXDN, ST5, DCLK1, SCARA5, EGFR, EGR1, ZFHX4, COL3A1, COMP, FNDC1, GALNT15, SULF1, GPX8 and IGFBP6 as set out in Table 5;

(iv) markers selected from COL1A2, COL5A1, COL16A1, COL14A1, COL4A2, PXDN, ST5, DCLK1, SCARA5, EGFR, EGR1 and ZFHX4 as set out in Table 9.

In an aspect of the method, a subset of at least 20 of the AC2 or AC3 markers are provided. In an aspect, a subset of at least 10 of the AC2 or AC3 markers are provided. At least 4, at least 5, at least 6, at least 7, at least 8, at least 9, at least 10, at least 11, at least 12, at least 13, at least 14, least 15, at least 16, at least 17, at least 18, at least 19, at least 20, at least 25, at least 30, at least 35, at least 40, at least 45, at least 50 of the AC2 or AC3 markers may provided.

In an embodiment, the subset of AC2 markers comprises naïve B cell gene markers and markers of developmental pathways for naïve B cells and leukocytes. In an embodiment, wherein the subset of AC3 markers comprises markers of cartilage morphogenesis, endochondral bone growth, extracellular matrix organization and sublining fibroblasts.

In another embodiment of the invention a set of one or more markers selected from COL1A2, COL5A1, COL16A1, COL14A1, COL4A2, PXDN, ST5, DCLK1, SCARA5, EGFR, EGR1, ZFHX4, COL3A1, COMP, FNDC1, GALNT15, SULF1, GPX8 and IGFBP6 is provided and/or utilized in accordance with the methods hereof. In an aspect, a set of one or more markers selected from COL1A2, COL5A1, COL16A1, COL14A1, COL4A2, PXDN, ST5, DCLK1, SCARA5, EGFR, EGR1 and ZFHX4 is provided and/or utilized in accordance with the methods hereof. In an aspect, a set of two or more, three or more, four or more, five or more, six or more, seven or more, eight or more, nine or more, ten or more, a dozen, at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least ten, a set of 5-10, a set of 3-5, a set of 5-7, a set of 3-7, a set of 5-8 selected from COL1A2, COL5A1, COL16A1, COL14A1, COL4A2, PXDN, ST5, DCLK1, SCARA5, EGFR, EGR1, ZFHX4, COL3A1, COMP, FNDC1, GALNT15, SULF1, GPX8 and IGFBP6 is provided and/or utilized in accordance with the methods hereof. In an aspect, a set of two or more, three or more, four or more, five or more, six or more, seven or more, eight or more, nine or more, ten or more, a dozen, at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least ten, a set of 5-10, a set of 3-5, a set of 5-7, a set of 3-7, a set of 5-8 selected from COL1A2, COL5A1, COL16A1, COL14A1, COL4A2, PXDN, ST5, DCLK1, SCARA5, EGFR, EGR1 and ZFHX4 is provided and/or utilized in accordance with the methods hereof.

The invention also provides a system or kit for predicting an impending RA flare comprising a set of markers as described and provided herein or a set of probes and/or antibodies for evaluating a set of markers as described and provided herein. As an example, a kit or system may include a set of markers or a set of probes and/or antibodies for evaluating a set of markers selected from or for a or any combination of:

(i) a subset of at least 20 markers from the AC2 markers provided in Table 7;

(ii) a subset of at least 20 markers from the AC3 markers provided in Table 8;

(iii) markers selected from COL1A2, COL5A1, COL16A1, COL14A1, COL4A2, PXDN, ST5, DCLK1, SCARA5, EGFR, EGR1, ZFHX4, COL3A1, COMP, FNDC1, GALNT15, SULF1, GPX8 and IGFBP6 as set out in Table 5;

(iv) markers selected from COL1A2, COL5A1, COL16A1, COL14A1, COL4A2, PXDN, ST5, DCLK1, SCARA5, EGFR, EGR1 and ZFHX4 as set out in Table 9.

The system or kit may further comprise a means for collection of the patient's blood by fingerstick.

Other objects and advantages will become apparent to those skilled in the art from a review of the ensuing detailed description, which proceeds with reference to the following illustrative drawings, and the attendant claims.

BRIEF DESCRIPTION OF THE DRAWINGS

The patent or patent application contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawing(s) will be provided by the U.S. Patent and Trademark Office upon request and payment of the necessary fee.

FIG. 1 depicts the study overview and validation of in-home assessments of disease activity and gene expression. A. Climical data collection and RNA analysis over time. Study overview of clinical data and sample collection over time. B. Clinical and patient reported assessments of disease activity. Correlation between disease activity scores measured in clinic (DAS28) and at home (RAPID3 questionnaire) from the index patient. Locally Weighted Smoothed Scatterplots Showing the Relationship between the Change in RAPID3 scores and DAS28 in the index patient. The solid line represents the point estimates and the gray area represents the 95 percent confidence intervals. C. Clinical blood counts and RNASeq-inferred blood counts. Neutrophil, lymphocyte, and monocyte counts measured from paired clinical complete blood counts from venipuncture blood draws and CIBERSORTx inferred blood counts from RNAseq data from finger stick blood draws (N=38 paired samples).

FIG. 2 provides clinical and transcriptional characteristics of RA flares in index patient. A. Index Patient disease activity over time. Disease activity (RAPID3 questionnaire, N=356), over the course of four years in index patient. Time points are colored according to disease activity category. B. Differential expression of genes in flare. Volcano plot of differential gene expression of flare (N=46) versus baseline (N=33), plotting statistical significance (−log 10(FDR)) against fold change (log 2(FC)) (gray points are non-significant genes, i.e., FDR>0.1, red indicates FDR<0.1 and log 2 fold change >0, blue indicates FDR<0.1 and log 2 fold change <0). Pathways enriched in significantly increased (C.) (Pathways increased in flare) or decreased genes (D.) (Pathways decreased in flare) in flare relative to baseline.

FIG. 3 provides transcriptional characteristics of immune activation prior to symptom onset in RA flares. A. Disease activity scores over time to flare (measured in days). Box represents disease activity from day −56 to +28 over time to flare. Vertical arrows (in A-D) represent start of flare. B. Hierarchical clustering of z scores of 2791 significantly differentially expressed genes over time to flare. Statistically significant clusters are labeled by color. AC2 and AC3 refer to clusters that changed antecedent to flare. C. Detailed representation of cluster 1, antecedent cluster 2 (AC2), and antecedent cluster 3 (AC3) genes from FIG. 3B over time to flare. D. Mean standardized cluster gene expression over time to flare. Light grey lines represent expression of individual genes in the cluster. Dashed horizontal line represents mean baseline gene expression (weeks −8 to −4). Dashed vertical line represents start of flare. E. Pathways enriched in clusters 1, AC2, and AC3.

FIG. 4 . PRIME cells express AC3 genes. A. Synovial cell subtype marker genes in clusters identified in blood (FIG. 3A). Enrichment scores of 200 single cell RNAseq marker genes from 18 synovial subset cell types. Dashed line represents threshold for significance (FDR<0.05 or −log 10 FDR>1.3). B. Mean standardized gene expression and 95% confidence intervals of genes common to synovial sublining fibroblasts (CD34+, DKK+ and HLA-DRA+ fibroblasts) and AC3 in blood over time to flare (dashed vertical line represents start of flare). Error bars represent confidence intervals. C. Venn diagram of AC3 genes that decrease during flare in 4 patients. D. Flow cytometry of blood samples from 19 RA patients and 18 healthy volunteers (HV). Percent PDPN+/CD45− cells of TOPRO−(live)/CD31− cells is presented. P value represents result of two sided t-test. E. Log₂ fold change of AC3 genes expressed in PRIME cells (flow sorted CD45−/CD31−/PDPN+ cells) versus hematopoietic cells (flow sorted CD45+) and Log₂ fold change of input cells (stained PBMC but not flow sorted) versus hematopoietic cells (flow sorted CD45+) as technical control for stress of flow sorting.

FIG. 5 provides a model of blood and synovial gene expression changes antecedent to and during RA flares. Inflammatory signals activate naïve B cells (AC2; FIG. 3C-E), which in turn activate PRIME cells (AC3; FIG. 3C-E) which harbor the signature of synovial sublining fibroblast genes (FIG. 4A). The model proposes that PRIME cells demarginate and are increased in blood prior to flare and then decrease (FIG. 4B) just after symptom onset; these cells or their progeny are increased in inflammatory RA synovium where they contribute to and may be sufficient to cause joint inflammation.

FIG. 6 depicts RNA quality and quantity by volume of fixative. 3 drops of blood harvested with a 21 guage lancet were added to a microtainer tube prefilled with either 250, 500 or 750 ul of PAX gene fixative. Samples were stored at room temperature for 3 days and then RNA was extracted using the PAX gene RNA kit and RIN scores and quantity of RNA was assessed using the Agilent 2100 Bioanalyzer picochip. Padj=ANOVA, followed by Dunnett's multiple comparisons test, using 250 ul as the reference group.

FIG. 7 depicts RNA quality and quantity by time at room temperature. 100 ul of whole blood was added to a microtainer tube prefilled with 250 ul PAX gene fixative and frozen after 2 hours, 3 days, or 7 days incubation at room temperature. RNA was extracted using the PAX gene RNA kit with scaled down washes and elutions and RIN scores and quantity of RNA was assessed using the Agilent 2100 BioAnalyzer RNA picochip. Padj=ANOVA, followed by Dunnett's multiple comparisons test, using Day 0 as the reference group.

FIG. 8 depicts RNA quality and quantity of fresh and mailed samples. 100 ul of whole blood was added to a microtainer tube prefilled with 250 ul PAX gene fixative and frozen after 2-hour incubation at room temperature or mailed. RNA was extracted using the PAX gene RNA kit and RIN scores and quantity of RNA was assessed using the Agilent 2100 BioAnalyzer RNA picochip.

FIG. 9 depicts RNA quality and quantity by volume of extraction and washes. 3 drops of blood harvested with a 21 guage lancet were added to a microtainer tube prefilled with 250 ul of PAX gene fixative. Samples were stored at room temperature for 3 days and then RNA was extracted using the PAXgeneRNA kit according to manufacturer's directions or with a scaled down version of the PAX protocol, using 25% of the recommended volumes for all washes and elutions. RIN scores and quantity of RNA was assessed using the Agilent 2100 BioAnalyzerRNA picochip. P=unpaired two-sided t test.

FIG. 10 depicts RNA quality and quantity with and without TriZol reagent extraction step. Mailed patient finger stick samples were stored in PAXgeneRNA buffer at −80′C. 142 samples had RNA extracted with PAXgeneRNA extraction with low volume washes, 13 samples were thawed and mixed with 700 ul Trizol-LS, and 250 ul chloroform. After centrifugation, the top layer was precipitated with isopropanol and glycogen and washed with 80% cold ethanol, centrifuged and the pellet was dried, resuspended in PBS and then purified using the Roche High Pure Isolation kit. P values represent significance of unpaired T tests.

FIG. 11 depicts Cycle Times for HbgA2, 18S RNA, and TNF alpha after GlobinZero depletion. Since ribosomal and hemoglobin RNA represent approximately 98% and 70% of the RNA in whole blood, respectively, we tested standard commercial kits for removing these RNAs prior to RNAseq. 4 ml heparinized blood, treated with 1 ug/ml LPS for one hour at 37° C. and placed 250 ul into 250 ul PAXgene fixative into replicate microtainer tubes. After RNA extraction samples were either left undepleted or treated with the globin zero depletion kit and then quantitative PCR was performed to test for hemoglobin A2, 18S RNA, or TNF alpha mRNA expression. GlobinZero kits depleted both hemoglobin A2 and 18S ribosomal RNA (increased mean cycle time from 11 to 28 and 10 to 30, respectively) with relative preservation of TNFalpha mRNA. P values represent results of ordinary one-way ANOVA with Tukey's multiple comparisons test.

FIG. 12 provides RNASeq QC metrics of RNA with various quality scores prepared with Illumina TruSeq or Kapa Hyper Prep Kits. A. (Left Panel): Distribution of mapping, uniquely mapping, and duplicate reads. B. (Right Panel): Distribution of tags assigned to UTR (untranslated region), intergenic, intronic, and CD5 (coding sequence) of whole blood RNA samples prepared with Illumina TruSeq or Kapa Hyper Prep Kits with various input RNA quality and quantity. The Illumina TruSeq library Prep demonstrated increased mapping to coding sequence and fewer intergenic reads and was ultimately used for downstream experiments.

FIG. 13 provides comparison of patient reported (RAPID3) and clinical (DAS28) disease activity scores of 4 patients. Paired RAPID3 scores and DAS28-CRP scores were collected from 91 clinic visits of 4 RA patients. The patient reported RAPID3 questionnaire was significantly correlated with clinician generated DAS28 score in all 4 patients.

FIG. 14 depicts clinical features of baseline, flare and on steroid treatment. RAPID3 questionnaire responses from 360 time points and DAS28 ESR, TJC, SJC, ESR, DAS28 CRP, platelet counts and absolute neutrophil counts from 43 clinic visits for one patient over four years. Time points are positioned and colored according to disease activity category: The first (left) set in each graph is baseline, the middle set in each graph is flare, and the third (right) set in each graph is steroid. Steroid treatment was defined as any time point when the patient took any dose of steroid that day, or if the calculated dose, using washout kinetics, was greater than 0.01 mg/ml. Samples acquired between two time points that met criteria for flare that did not meet flare criteria were still categorized as flare up until treatment with steroid. TJC indicates tender joint count. SJC indicates swollen joint count. P values represent ANOVA across three disease categories. Flare was associated with significantly increased RAPID3, DAS28 ESR, TJC, SJC, ESR, DAS28CRP, platelets and neutrophils.

FIG. 15 depicts that differentially expressed flare genes are reproducibly altered in repeated flares. A. Index patient disease activity (RAPID3) over time. Top panel dots are colored by disease activity assignment. Bottom panel dots are colored according to clinical flare event number. B. Unsupervised hierarchical clustering of genes differentially expressed between baseline and flare. Top bar indicates samples colored according to disease activity assignment. Bottom bar indicates samples colored according to clinical flare event number. Data shows differentially expressed flare genes are represented by multiple clinical events.

FIG. 16 provides deconvolution of blood cell types over time to flare. Mean cell type trajectories of A. ABIS inferred cell types, and B. CIBERSORTx inferred cell types over time to flare are plotted (excluding those that were 0 all throughout) showing the mean score with standard error of the mean as a ribbon. These data independently confirm data in main FIG. 4A identifying activation of B cells in AC2.

FIG. 17 depicts that distinct analysis approaches identify activation of naïve B cells in blood 2 weeks prior to flare. A. CIBERSORTx inferred naïve B cells by week to flare. B. ABIS inferred naïve B cells by week to flare. C. Mean expression of 190 synovial single cell RNAseq naïve B cell marker genes by week to flare. D. IGHM (blue/top) and IGHD (red/bottom) gene expression by week to flare. Dashed line indicates first day of symptoms of RA flare, red arrows indicate peak in B cell signature 2 weeks prior to flare.

FIG. 18 provides mean standardized gene expression of genes common to synovial sublining fibroblasts (CD34+, DKK+, and HLA-DR+fibroblasts) and AC3 in blood over time to flare. Light gray lines represent the expression of individual genes over time to flare in patient 1 over all flares.

FIG. 19 depicts gating strategy for quantification of PRIME cells in blood samples. Previously frozen peripheral blood mononuclear cells were thawed and stained with antibodies to CD31, PDPN, and CD45 as well as TOPRO. Live CD31− cells were gated and PDPN+, CD45− cells were enumerated.

FIG. 20 demonstrates PRIME cells are nucleated. PBMC of RA donor was stained with CD45/CD31/PDPN and either TOPRO (Not Permeabilized) or permeabilization and TOPRO (Permeabilized) and assessed by flow cytometry. PRIME cells were gated as CD45−/CD31−/PDPN+ cells and TOPRO staining of permeabilized and not permeabilized cells is presented. The increased fluorescence of TOPRO in the permeabilized PRIME cells indicates the presence of double stranded nucleic acid.

FIG. 21 depicts that sorted PRIME cells express synovial fibroblast genes. Log 2 fold change of various synovial single cell RNAseq marker genes in PRIME cells (flow sorted CD45−/CD31−/PDPN+ cells) versus hematopoietic cells (flow sorted CD45+) and Log 2 fold change of Input cells (stained PBMC but not flow sorted) versus hematopoietic cells (flow sorted CD45+) as technical control for stress of flow sorting. These data show that single cell marker genes of fibroblasts (SC-F1, SC-F2, SC-F3, SC-F4) but not B cells (SC-B1-4), macrophages (SC-M1-4), or T cells (SC-T1-6) are enriched in sorted PRIME cells. Fibroblast genes (as marked) were the only set of synovial cell marker genes enriched in PRIME cells.

FIG. 22 depicts that sorted PRIME cells express classic synovial fibroblast genes. Volcano plot of Log 10(−padj) vs Log 2 fold change of PRIME cells (flow sorted CD45−/CD31−/PDPN+ cells) versus hematopoietic cells (flow sorted CD45+). Classic fibroblast genes are significantly increased in PRIME cells relative to hematopoietic cells.

DETAILED DESCRIPTION

In accordance with the present invention there may be employed conventional molecular biology, microbiology, and recombinant DNA techniques within the skill of the art. Such techniques are explained fully in the literature. See, e.g., Sambrook et al, “Molecular Cloning: A Laboratory Manual” (1989); “Current Protocols in Molecular Biology” Volumes I-II [Ausubel, R. M., ed. (1994)]; “Cell Biology: A Laboratory Handbook” Volumes I-III [J. E. Celis, ed. (1994))]; “Current Protocols in Immunology” Volumes I-II [Coligan, J. E., ed. (1994)]; “Oligonucleotide Synthesis” (M. J. Gait ed. 1984); “Nucleic Acid Hybridization” [B. D. Hames & S. J. Higgins eds. (1985)]; “Transcription And Translation” [B. D. Hames & S. J. Higgins, eds. (1984)]; “Animal Cell Culture” [R. I. Freshney, ed. (1986)]; “Immobilized Cells And Enzymes” [IRL Press, (1986)]; B. Perbal, “A Practical Guide To Molecular Cloning” (1984).

Therefore, if appearing herein, the following terms shall have the definitions set out below.

A. Terminology

The term “rheumatoid arthritis” or “RA” refers to a chronic disease, which is immune-mediated and inflammatory and is an autoimmune disorder, affecting the lining of joints that causes joint pain, stiffness, swelling and decreased movement of the joints and can eventually result in bone erosion and joint deformity. RA is a systemic autoimmune disease characterized by the simultaneous inflammation of the synovium of multiple joints.

An “RA flare” or “flare” refers to a surge in immune-mediated and/or inflammatory activity that is periodically experienced by a patient(s) with RA. During a flare, the level of fatigue and joint symptoms such as pain, swelling, and stiffness temporarily increase. Flares are periods of increased disease activity during which people's arthritis symptoms, which typically include joint pain, swelling, and stiffness, are more severe. An RA flare can involve an exacerbation of any symptom of the disease, but most commonly includes intense stiffness in the joints. People with RA report these common symptoms of flares: increased stiffness in joints, pain throughout the entire body, increased difficulty doing everyday tasks, swelling, such as causing shoes not to fit, intense fatigue, flu-like symptoms.

The term “antibody” describes an immunoglobulin whether natural or partly or wholly synthetically produced. The term also covers any polypeptide or protein having a binding domain which is, or is homologous to, an antibody binding domain. CDR grafted antibodies are also contemplated by this term. An “antibody” is any immunoglobulin, including antibodies and fragments thereof, that binds a specific epitope. The term encompasses polyclonal, monoclonal, and chimeric antibodies. The term “antibody(ies)” includes a wild type immunoglobulin (Ig) molecule, generally comprising four full length polypeptide chains, two heavy (H) chains and two light (L) chains, or an equivalent Ig homologue thereof (e.g., a camelid nanobody, which comprises only a heavy chain); including full length functional mutants, variants, or derivatives thereof, which retain the essential epitope binding features of an Ig molecule, and including dual specific, bispecific, multispecific, and dual variable domain antibodies; Immunoglobulin molecules can be of any class (e.g., IgG, IgE, IgM, IgD, IgA, and IgY), or subclass (e.g., IgG1, IgG2, IgG3, IgG4, IgA1, and IgA2). Also included within the meaning of the term “antibody” are any “antibody fragment”.

An “antibody fragment” means a molecule comprising at least one polypeptide chain that is not full length, including (i) a Fab fragment, which is a monovalent fragment consisting of the variable light (VL), variable heavy (VH), constant light (CL) and constant heavy 1 (CH1) domains; (ii) a F(ab′)2 fragment, which is a bivalent fragment comprising two Fab fragments linked by a disulfide bridge at the hinge region; (iii) a heavy chain portion of an Fab (Fd) fragment, which consists of the VH and CH1 domains; (iv) a variable fragment (Fv), which consists of the VL and VH domains of a single arm of an antibody, (v) a domain antibody (dAb) fragment, which comprises a single variable domain (Ward, E. S. et al., Nature 341, 544-546 (1989)); (vi) a camelid antibody; (vii) an isolated complementarity determining region (CDR); (viii) a Single Chain Fv Fragment wherein a VH domain and a VL domain are linked by a peptide linker which allows the two domains to associate to form an antigen binding site (Bird et al, Science, 242, 423-426, 1988; Huston et al, PNAS USA, 85, 5879-5883, 1988); (ix) a diabody, which is a bivalent, bispecific antibody in which VH and VL domains are expressed on a single polypeptide chain, but using a linker that is too short to allow for pairing between the two domains on the same chain, thereby forcing the domains to pair with the complementarity domains of another chain and creating two antigen binding sites (WO94/13804; P. Holliger et al Proc. Natl. Acad. Sci. USA 90 6444-6448, (1993)); and (x) a linear antibody, which comprises a pair of tandem Fv segments (VH-CH1-VH-CH1) which, together with complementarity light chain polypeptides, form a pair of antigen binding regions; (xi) multivalent antibody fragments (scFv dimers, trimers and/or tetramers (Power and Hudson, J Immunol. Methods 242: 193-204 9 (2000)); (xii) a minibody, which is a bivalent molecule comprised of scFv fused to constant immunoglobulin domains, CH3 or CH4, wherein the constant CH3 or CH4 domains serve as dimerization domains (Olafsen T et al (2004) Prot Eng Des Sel 17(4):315-323; Hollinger P and Hudson P J (2005) Nature Biotech 23(9):1126-1136); and (xiii) other non-full length portions of heavy and/or light chains, or mutants, variants, or derivatives thereof, alone or in any combination.

As antibodies can be modified in a number of ways, the term “antibody” should be construed as covering any specific binding member or substance having a binding domain with the required specificity. Thus, this term covers antibody fragments, derivatives, functional equivalents and homologues of antibodies, including any polypeptide comprising an immunoglobulin binding domain, whether natural or wholly or partially synthetic. Chimeric molecules comprising an immunoglobulin binding domain, or equivalent, fused to another polypeptide are therefore included.

The term “adjuvant(s)” describes a substance, compound, agent or material useful for improving an immune response or immune cell or component stimulation, and may in some instances be combined with any particular antigen in an immunological, pharmaceutical or vaccine composition. Adjuvants can be used to increase the amount of antibody and effector T cells produced and to reduce the quantity of antigen or immune stimulant or modulator and the frequency of injection. An adjuvant can serve as a tissue depot that slowly releases the antigen and also as a lymphoid system activator that non-specifically enhances the immune response. In a preferred aspect an adjuvant is physiologically and/or pharmaceutically acceptable in a mammal, particularly a human.

The term “specific” may be used to refer to the situation in which one member of a specific binding pair will not show any significant binding to molecules other than its specific binding partner(s). The term is also applicable where e.g. an antigen binding domain is specific for a particular epitope which is carried by a number of antigens, in which case the specific binding member carrying the antigen binding domain will be able to bind to the various antigens carrying the epitope.

The term “comprise” generally used in the sense of include, that is to say permitting the presence of one or more features or components. The term “consisting essentially of” refers to a product, such as a peptide sequence, of a defined number of residues which is not covalently attached to a larger product.

The term “oligonucleotide,” as used herein in referring to a probe of use the present invention, is defined as a molecule comprised of two or more ribonucleotides, preferably more than three. Its exact size will depend upon many factors which, in turn, depend upon the ultimate function and use of the oligonucleotide. The term “primer” as used herein refers to an oligonucleotide, which is capable of acting as a point of initiation of synthesis when placed under conditions in which synthesis of a primer extension product, which is complementary to a nucleic acid strand, is induced, i.e., in the presence of nucleotides and an inducing agent such as a DNA polymerase and at a suitable temperature and pH. The primer may be either single-stranded or double-stranded and must be sufficiently long to prime the synthesis of the desired extension product in the presence of the inducing agent. The exact length of the primer will depend upon many factors, including temperature, source of primer and use of the method. For example, for diagnostic applications, depending on the complexity of the target sequence, the oligonucleotide primer typically contains 15-25 or more nucleotides, although it may contain fewer nucleotides.

The term “agent” means any molecule, including polypeptides, antibodies, polynucleotides, chemical compounds and small molecules. In particular the term agent includes compounds such as test compounds or drug candidate compounds.

The term “assay” means any process used to measure a specific property of a compound. A “screening assay” means a process used to characterize or select compounds based upon their activity from a collection of compounds.

The term “protein” is used herein to mean protein, polypeptide, oligopeptide or peptide. The terms “protein marker”, “biomarker” or “protein marker of impending flare” are used herein to refer to proteins associated with or predictive or which precede specific diseases or conditions or symptoms, including proteins from or associated with aspects, cells or tissues affected by a disease or condition or symptom. In accordance with the present invention, the increase in marker expression relative to that detected or characteristic of a subject/s without overt organic RA disease or significant joint or pain symptoms or without an impending flare or a normal, healthy subject/s (control/controls) is positively correlated with, indicative of, or diagnostic for the impending presence or flare or flare-up of a disease or condition or symptoms thereof particularly an exacerbation of disease or symptoms, such as rheumatoid arthritis and particularly an RA flare, in a patient.

As used herein, the terms “increase” in marker expression or “differential expression” of a marker refer to a statistically significant increase or presence. The term statistically significant is used in the art to refer to the likelihood that a result or relationship is caused by something other than mere random chance. Statistical hypothesis testing is traditionally employed to determine if a result is statistically significant or not. Such testing provides a “p-value” representing the probability that random chance could explain the result. In general, a 5% or lower p-value is considered to be statistically significant.

A skilled practitioner would, moreover, appreciate that a relative increase or decrease in a particular protein (a protein marker) or a particular RNA (an RNA marker) in a sample alone may be weakly indicative or predictive of disease, but may not be diagnostic per se, if noted as a single determinant. If, however, a plurality of such single determinants are noted in a biological sample, the combined detection of several, even weakly indicative, determinants may serve to identify a strong combinatorial diagnostic indicator of impending disease or symtpomatic disease aspects, such as impending RA flare. Furthermore, the single protein/determinant need not approach the threshold of weak diagnostic by itself but in combination with the detection of an increase of another protein or proteins or RNA or RNAs (other markers) may serve as a strong combinatorial diagnostic indication of an impending disease state. Accordingly, also encompassed herein are combinatorial diagnostic indicators or combinatorial markers that are associated with a particular disease or an impending disease and not observed in healthy subjects or patients with other diseases.

Accordingly, selected sets of one, two, three, several, at least 10, about 10, a dozen, 10-15, about 20, at least 20, 25, 30, about 30 and more, etc of the markers of this invention (up to the number equivalent to all of the markers, or all in a set of markers, including any intervening number, in whole number increments, e.g., 1, 2, 3, 4, 5, 6 . . . ) can be used as diagnostic indicators and predictors of an impending flare for methods and/or in kits described herein. In one embodiment, larger numbers of the markers identified herein are used in methods or kits of the invention, since the accuracy of the method or kit may improve as the number of markers screened increases. With respect to aspects of the invention pertaining to evaluating therapeutic efficacy, the methods and kits of the present invention include evaluating whether administration of a therapeutic composition causes a change, either a transient change or a long term change, in expression of one or more of the markers; in expression of two or more of the markers; in expression of three or more of the biomarkers; in expression of four or more of the biomarkers; in expression of five or more of the biomarkers, in expression of six or more of the biomarkers, etc.

As an example, a straightforward identification of a protein marker or an RNA marker is the presence of a protein or RNA associated with an impending disease or condition and not with other conditions that might be clinically confused with the disease under consideration. Variations to this scenario include the situation wherein a marker is present in an increased quantity compared to other conditions or controls. Although not a protein marker, an example is the presence of glucose in the blood in high quantities in diabetics compared to normal individuals who have glucose present but not in elevated quantities. A variation is where the functional marker is not just one protein but two or more in combination that can be quantitatively different, wherein the ensemble defines its marker potential.

In some embodiments, a marker of the invention is a member of a biological pathway. As used herein, the term “precursor” or “successor” refers to molecules that precede or follow the marker in the biological pathway. Thus, once a marker is identified as a member of one or more biological pathways, the present invention can include additional members of the biological pathway that come before (are upstream of or a precursor of) or follow (are downstream of) the marker. Such identification of biological pathways and their members is within the skill of one in the art.

Also encompassed herein is the analysis of markers identified and listed in the tables presented herein to identify metabolic pathways implicated in the pathogenesis, maintenance, and/or progression of a disease or an impending disease or system or flare. Such analyses may utilize a variety of software programs or approaches known and available to the skilled artisan. Multiple hits in a particular metabolic pathway underscore the potential importance of the pathway for the disease and direct therapeutic intervention toward appropriate modulation of same. Accordingly, the present methods encompass such analyses and the identification of metabolic pathways of potential significance in a particular disease or impending disease aspect or symptom. Knowing that, for example, activation of a metabolic pathway appears to be linked or associated with a particular disease or impending symptom presents the opportunity to test pharmaceutical modulators of the pathway (i.e., inhibitors) to determine if such modulators could be used as therapeutics for treatment of patients with the disease or impending disease or symptoms. This and these aspects are illustrated and described herein including in the examples.

Polypeptide or protein markers and RNA(s) or RNA markers may be isolated or evaluated by any suitable method known in the art. Proteins or RNAs can be purified or assayed by standard methods known in the art such as via immunoassay, ELISA, nucleic acid probes, primers, oligonucleotides, antibody affinity methods, RNA sequencing etc. In one embodiment, polypeptide and metabolite markers may be isolated from a biological sample using standard techniques known in the art, for example, affinity purification using substrate-bound antibodies that specifically bind to the marker. As described herein, immunoaffinity depletion of abundant RNA(s) or proteins (with masking potential) enhances coverage and detection of low abundance proteins or RNA(s).

Antibodies immunospecific for any one of the markers provided herein may be known and available to the public and may be accessed via the scientific community or purchased from a commercial vendor. Readily searchable databases or web browsers may be utilized for example for identifying potential suppliers for such antibodies.

In accordance with the present disclosure, the tables present information with which an ordinarily skilled practitioner can access the amino acid sequences of the proteins and RNAs identified herein as markers, as well as nucleic acid sequences encoding same. A stepwise protocol or means for identification of the sequences listed in the tables presented herein may include the artisan accessing one of the publicly available databases and entering the ensemble number or gene name or symbol to identify the sequence and relevant marker information. Such information may be used to design probes for detection of any of the proteins, genes, RNAs listed therein or to identify commercially available probes or antibodies therefore or thereof. Primers for detection of nucleic acid sequences encoding any of the proteins listed in the tables presented herein are also envisioned as are primers for PCR including RT PCR. Such primers may be used to detect RNA expression levels (including relative increases or decreases as compared to controls) of a marker relevant to the invention. The design of primers for detecting expression levels of RNA (e.g., mRNA) of a marker or markers listed herein is a matter of routine practice with the nucleic acid sequence in hand as provided by publicly available websites such as those mentioned above. Such probes and primers are useful for the kits described herein.

The term “preventing” or “prevention” refers to a reduction in risk of acquiring or developing a disease or disorder (i.e., causing at least one of the clinical symptoms of the disease not to develop) in a subject that may be exposed to a disease-causing agent, or predisposed to the disease in advance of disease onset. The term “prophylaxis” is related to and encompassed in the term ‘prevention’, and refers to a measure or procedure the purpose of which is to prevent, rather than to treat or cure a disease. Non-limiting examples of prophylactic measures may include the administration of vaccines; the administration of low molecular weight heparin to hospital patients at risk for thrombosis due, for example, to immobilization; and the administration of an anti-malarial agent such as chloroquine, in advance of a visit to a geographical region where malaria is endemic or the risk of contracting malaria is high.

“Therapeutically effective amount” means that amount of a drug, compound, antibody, or pharmaceutical agent that will elicit the biological or medical response of a subject that is being sought by a medical doctor or other clinician. In particular, with regard to gram-positive bacterial infections and growth of gram-positive bacteria, the term “effective amount” is intended to include an effective amount of a compound or agent that will bring about a biologically meaningful decrease in the amount of or extent of disease or flare free time period and or increase in length of a subject's survival or period disease-free or in remission or free of flare(s). The phrase “therapeutically effective amount” is used herein to mean an amount sufficient to prevent, and preferably reduce by at least about 30 percent, more preferably by at least 50 percent, most preferably by at least 90 percent, a clinically significant change, or enhanced survival or disease-free period by at least about 30 percent, more preferably by at least 50 percent, most preferably by at least 90 percent.

The term “treating” or “treatment” of any disease, condition, or infection refers, in one embodiment, to ameliorating the disease or infection (i.e., arresting the disease or growth of the infectious agent or bacteria or reducing the manifestation, extent or severity of at least one of the clinical symptoms thereof). In another embodiment “treating” or “treatment” refers to ameliorating at least one physical parameter, which may not be discernible by the subject. In another embodiment, “treating” or “treatment” refers to modulating the disease or infection, either physically, (e.g., stabilization of a discernible symptom), physiologically, (e.g., stabilization of a physical parameter), or both. In a further embodiment, “treating” or “treatment” relates to slowing the progression of a disease or reducing an infection.

The phrase “pharmaceutically acceptable” refers to molecular entities and compositions that are physiologically tolerable and do not typically produce an allergic or similar untoward reaction, such as gastric upset, dizziness and the like, when administered to a human.

As used herein, “pg” means picogram, “ng” means nanogram, “ug” or “pg” mean microgram, “mg” means milligram, “ul” or “pl” mean microliter, “ml” means milliliter, “l” means liter.

B. Detailed Disclosure

The invention relates to and provides previously unidentified and unrecognized markers, particularly RNA markers and protein markers, which are indicators and antecedents of an impending rheumatoid arthritis (RA) flare. The markers are differentially expressed or preferentially expressed prior to an RA flare in an RA patient and provide markers which can predict an impending flare and can be utilized to implement and prescribe treatment and therapy to a patient.

Arthritis is a disease that may cause damage to the healthy cartilage of joints, leading to degenerative changes, loss of function and joint instability. Inflammatory arthritis describes conditions characterized by pain, swelling, tenderness and warmth in the joints, as well as morning stiffness that lasts for more than an hour. An increase of cytokines leads to degradation of articular cartilage and a decrease of growth factors which induce chondrogenesis in inflammatory arthritis. The most common inflammatory arthritis associated disorders rheumatoid arthritis (RA), psoriatic arthritis (PsA), systemic lupus erythernatosus (SLE, lupus), ankylosing spondylitis (AS), and gouty arthritis (gout). Arthritis damages the cartilage within joints, resulting in degenerative changes, including loss of function and joint instability. Ankylosing spondylitis (AS) is a chronic inflammatory condition affecting the spine and bone-to-tendon attachment area within the sacroiliac joint leading to back pain and progressive spinal stiffness. Rheumatoid arthritis is a chronic, systemic autoimmune disease characterized by the simultaneous inflammation of the synovium of multiple joints, leading to joint damage (e.g., destruction, deformation and disability). Gout is a chronic inflammatory disease that causes an alteration of joints resulting in severe pain and is associated with an accumulation of uric acid within the body resulting from dysregulated purine metabolism, causing recurrent paroxysmal inflammation in the joints. Allopurinol and febuxostat are the primary treatment options for individuals with gout.

Various disease modifying agents for treating or modifying RA, including for management and alleviation of RA flares, are known and in use climactically. Nonsteroidal anti-inflammatory drugs (NSAIDs) or conventional disease-modifying antirheumatic drug (DMARDs) have been used for the treatment of these inflammatory diseases, particularly RA. More recently, biologic DMARDs have been introduced with excellent results. NSAIDs include non-prescription drugs acetylsalicylate (aspirin), ibuprofen (Advil, Motrin IB) and naproxen sodium (Aleve, Naprosyn) and prescription NSAIDs such as etodolac (Lodine) and diclofenac (Voltaren). Steroids are anti-inflammatory or immunosuppressants agents and are prescribed for more severe RA or when RA symptoms flare to ease joint pain and stiffness. Examples include glucocotricosteroids or corticosteroids such as prednisone, cortisone and methylprednisolone. DMARDs are prescribed and utilized to slow the progression of RA and save joints and other tissues from permanent damage. Common conventional DMARDs include methotrexate (Trexall, Otrexup), leflunomide (Arava), hydroxychloroquine (Plaquenil) and sulfasalazine (Azulfidine). DMARDs curb the overactive immune system in RA but aren't selective in their targets. Biologics—genetically engineered proteins which target a specific aspect or part of the immune system and act as immunosuppressants—are an increasingly important component in treatment of RA and are commonly denoted biologic DMARDs or bDMARDs. Biologics include abatacept (Orencia), adalimumab (Humira), anakinra (Kineret), baricitinib (Olumiant), certolizumab (Cimzia), etanercept (Enbrel), golimumab (Simponi), infliximab (Remicade), rituximab (Rituxan), sarilumab (Kevzara), tocilizumab (Actemra) and tofacitinib (Xeljanz). Adalimumab, etanercept, infliximab, golimumab and certolizumab target tumor necrosis factor (TNF). Rituximab is effective against B cells. Anakinra blocks the action of interleukin-1 (IL-1), a master cytokine. Abatacept targets T cells. Biologic DMARDs are usually most effective when paired with a nonbiologic DMARD, such as methotrexate. New DMARD drugs which are specific in their targets but are not biologics include oral small molecule Janus kinase (JAK) inhibitors such as tofacitinib (Xeljanz and Xeljanz XR), baricitinib (Olumiant), and upadacitinib (Rinvoq).

The American College of Rheumatology (ACR) has recommendations for RA patient treatment given various disease parameters (e.g., Singh J et al (2016) Arthritis Rheumatolo 68:1-26). Disease activity scales are utilized in managing RA patients and choosing appropriate treatment modalities, including the routine assessment of patient index data 3 (RAPID3) and the disease activity score 28 (DAS28) (Fransen, J et al (2003) Arthritis Rheum 49 Suppl:S214-24), which incorporates tenderness and swelling from 28 joints, erythrocyte sedimentation rate (ESR) and patient global assessment of disease activity, both of which have been utilized in studies described herein. Additional assessment instruments include Patient Activity Sale (PAS) or PASII (Wolfe, F et al (2005) J Rheumatol 32:2410-5), Clinical Disease Activity Index (CDAI) (Aletaha, D et al (2005) Arthritis Res Ther 7:R796-806) and Simplified Disease Activit Index (SDAI) (Smolen, J S et al (2003) Rheumatology 42:244-57). Each of these scales and assessments are applicable in treatment once a patient has symptomatic aspects or indicators of a flare or of disease. These scales cannot predict a flare, they are indicators of a flare or of exacerbation of disease.

RA patients are not able to predict a flare and are therefore subject to unpredictable exacerbations of disease and disease-associated symptoms and continual, progressive joint damage. The availability of dependable markers of impending flare(s), which can be readily and reliably assessed, particularly without significant clinical intervention, would significantly impact the treatment and management of RA patients and reduce the impact and long-term effects of the disease.

Toward that end, the invention provides a first set of markers that are expressed two weeks or about two weeks prior to an RA flare. The timing before flare can have a margin of error of about a week or 7 days. Referring to the studies provided herein, patients symptoms were assessed using a questionnaire that asked about how they were doing over the past week, therefore there is a possible 7 day margin of error in timing. For instance, given the questionnaire, the researchers could not necessarily discriminate between symptoms that started that day (or on day 1) vs 6 days earlier, or about a week or up to 7 days earlier. Therefore, the timing of the first set of markers is about two weeks, with a margin of error up to an additional 7 days, therefore up to 3 weeks or a week up to three weeks or 7-21 days. A first set of markers can be identified and characterized in a patient sample, particularly a blood sample, including a finger stick sample of blood, two weeks or about two weeks, about 14 days, approximately 14 days, more than one week, more than 12 days, more than 10 days, about 10-14 days, about 12-14 days prior to an RA flare, with a margin of error in each instance of up to about a week or 7 days, therefore, with a margin of error up to three weeks, at least a week, about two or three weeks, two or three weeks, about 7-21 days, up to 21 days, at least 7-10 days, about two to three weeks prior to an RA flare. These actecedent markers, particularly denoted AC2 markers, are provided in Table 7.

Another and second set of markers are provided that are expressed one week or about one week, or about 7 days, approximately 7 days, prior to an RA flare. The timing before flare can have a margin of error of about a week or 7 days. Referring to the studies provided herein, patients symptoms were assessed using a questionnaire that asked about how they were doing over the past week, therefore there is a possible 7 day margin of error in timing. For instance, given the questionnaire, the researchers could not necessarily discriminate between symptoms that started that day (or on day 1) vs 6 days earlier, or about a week or up to 7 days earlier. The second set of markers can be identified and characterized in a patient sample, particularly a blood sample, including a finger stick sample of blood, about one week, or about 7 days, approximately 7 days, about 5-7 days prior to an RA flare, with a margin of error in each instance of up to about a week or 7 days, therefore, with a margin of error up to two weeks, up to 14 days, 0-14 days, about one to two weeks, at least a week, about a week to 10 days, 7-14 days, 5-14 days prior to a flare. These antecedent markers, particularly denoted AC3 markers, are provided in Table 8. The set of AC2 markers or the first set of markers are expressed further out from a flare and more than a week before flare, up to three weeks prior to an RA flaree, while the set of AC3 markers or the second set of markers are expressed thereafter or closer to a flare and about a week or up to two weeks prior to a flare.

In an aspect, the AC3 markers, or one or more AC3 marker, or AC3 markers which are sublining fibroblast genes, are decreased during flare or after the commencement of a flare or once a patient experiences physical indicators or symptoms of a flare. Physical indicators or symptoms of a flare may be selected from stiffness in joints, pain throughout the body, increased difficulty doing everyday tasks, swelling, fatigue and flu-like symptoms. In an aspect, synovial cell marker genes or proteins among the AC3 markers and Table 8 are selected. A flare(s) may be evaluated by recognition of the symptoms in a patient and/or utilizing any recognized disease activity scales, including as described and provided herein.

RNA markers and protein markers of impending flare which are particularly selected for determining and predicting impending RA flares are provided in Table 9. The markers COL1A2, COL5A1, COL16A1, COL14A1, COL4A2, PXDN, ST5, DCLK1, SCARA5, EGFR, EGR1 and ZFHX4. RNAs or their encoded proteins selected from COL1A2, COL5A1, COL16A1, COL14A1, COL4A2, PXDN, ST5, DCLK1, SCARA5, EGFR, EGR1 and ZFHX4 are expressed one week or about one week, or about 7 days, approximately 7 days, about 5-7 days, at least 5 days prior to an RA flare. Markers selected from COL1A2, COL5A1, COL16A1, COL14A1, COL4A2, PXDN, ST5, DCLK1, SCARA5, EGFR, EGR1 and ZFHX4. RNAs or their encoded proteins selected from COL1A2, COL5A1, COL16A1, COL14A1, COL4A2, PXDN, ST5, DCLK1, SCARA5, EGFR, EGR1 and ZFHX4 are expressed one week or about one week, or about 7 days, approximately 7 days, about 5-7 days, at least 5 days prior to an RA flare. In particular, the markers are differentially expressed in a patient prior to a flare. Markers selected from COL1A2, COL5A1, COL16A1, COL14A1, COL4A2, PXDN, ST5, DCLK1, SCARA5, EGFR, EGR1 and ZFHX4. RNAs or their encoded proteins selected from COL1A2, COL5A1, COL16A1, COL14A1, COL4A2, PXDN, ST5, DCLK1, SCARA5, EGFR, EGR1 and ZFHX4 are differentially expressed, their expression is increased or higher relative to other markers or proteins, or their expression is significantly increased relative to expression in a normal sample or a sample from an individual that does not have RA or any other recognized inflammatory or autoimmune disease, one week or about one week, or about 7 days, approximately 7 days, about 5-7 days, at least 5 days prior to an RA flare. As noted above, the margin of error in timing may be up to a week or 7 days. Therefore expression of these markers selected from COL1A2, COL5A1, COL16A1, COL14A1, COL4A2, PXDN, ST5, DCLK1, SCARA5, EGFR, EGR1 and ZFHX4. RNAs or their encoded proteins selected from COL1A2, COL5A1, COL16A1, COL14A1, COL4A2, PXDN, ST5, DCLK1, SCARA5, EGFR, EGR1 and ZFHX4 maybe increased one top two weeks or 0-14 days, or about a week or two prior to a flare. Expression of RNAs or their encoded proteins selected from COL1A2, COL5A1, COL16A1, COL14A1, COL4A2, PXDN, ST5, DCLK1, SCARA5, EGFR, EGR1 and ZFHX4 are reduced, significantly decreased, nearly absent, or absent in peripheral blood during an RA flare. Expression of RNAs or their encoded proteins selected from COL1A2, COL5A1, COL16A1, COL14A1, COL4A2, PXDN, ST5, DCLK1, SCARA5, EGFR, EGR1 and ZFHX4 are reduced, significantly decreased, or nearly absent peripheral blood during an RA flare in comparison to their expression prior to a flare, particularly their expression about a week, or up to two weeks, prior to a flare.

RNA markers and transcripts or protein markers common to synovial sublining fibroblasts which are markers of impending flare and are capable of predicting or determining an impending flare as set out in Table 5. The markers comprise COL1A2, COL5A1, COL16A1, COL14A1, COL4A2, PXDN, ST5, DCLK1, SCARA5, EGFR, EGR1, ZFHX4, COL3A1, COMP, FNDC1, GALNT15, SULF1, GPX8 and IGFBP6. The markers are COL1A2, COL5A1, COL16A1, COL14A1, COL4A2, PXDN, ST5, DCLK1, SCARA5, EGFR, EGR1, ZFHX4, COL3A1, COMP, FNDC1, GALNT15, SULF1, GPX8 and IGFBP6. The markers are selected from COL1A2, COL5A1, COL16A1, COL14A1, COL4A2, PXDN, ST5, DCLK1, SCARA5, EGFR, EGR1, ZFHX4, COL3A1, COMP, FNDC1, GALNT15, SULF1, GPX8 and IGFBP6. RNAs or their encoded proteins selected from COL1A2, COL5A1, COL16A1, COL14A1, COL4A2, PXDN, ST5, DCLK1, SCARA5, EGFR, EGR1, ZFHX4, COL3A1, COMP, FNDC1, GALNT15, SULF1, GPX8 and IGFBP6 are expressed one week or about one week, or about 7 days, approximately 7 days, about 5-7 days, at least 5 days, prior to an RA flare. As noted above, the margin of error in timing may be up to a week or 7 days. Therefore, expression of these markers of impending flare may be found or evident a week or up to two weeks, at least about a week, about 0-14 days, up to two weeks, 5-14 days prior to a flare. Expression of RNAs or their encoded proteins selected from COL1A2, COL5A1, COL16A1, COL14A1, COL4A2, PXDN, ST5, DCLK1, SCARA5, EGFR, EGR1, ZFHX4, COL3A1, COMP, FNDC1, GALNT15, SULF1, GPX8 and IGFBP6 are reduced, significantly decreased, nearly absent, or absent in peripheral blood during an RA flare.

In accordance with the invention herein, the recognition of unique markers in peripheral blood has led to the identification and characterization of a distinctive and specific cell or cell type type circulating in the blood of a patient or individual prior to a flare. This unique and specific blood circulating cell is an novel indicator of an impending RA flare. The invention includes a unique blood circulating cell, denoted a Pre-Inflammatory mesenchymal (PRIME) cell, which has been identified and characterized as circulating in peripheral blood in a patient, particularly an RA patient, particularly a human, prior to an RA flare. The presence of this cell in peripheral blood indicates that an RA flare will occur or become evident by way of one or more patient symptom(s). The cell can be identified in patient peripheral blood about one week, one week, about 7 days, about 5-8 days, about 5-7 days, 5-8 days, 5-7 days, about 4-7 days, 4-7 days, about 3-7 days, 3-7 days prior to an RA flare. The cell can be identified in patient peripheral blood about one week, one week, about 7 days, about 5-8 days, about 5-7 days, 5-8 days, 5-7 days, about 4-7 days, 4-7 days, about 3-7 days, 3-7 days prior to inflammation of one or more joints or pain in one or more joints in a patient. As noted above, the margin of error in timing may be up to a week or about 7 days. Therefore, the cell can be identified in patient peripheral blood about one week to about 2 weeks, about 7-14 days, up to 14 days, 0-14 days, about 3-14 days, about 5-14 days prior to an RA flare In an embodiment, PRIME cell(s) can be identified and characterized as a CD45−CD31−PDPN+ cell, particularly as a CD45−CD31−PDPN+ cell in peripheral blood. In another embodiment, PRIME cell(s) can be identified and characterized as a CD45−CD31−PDPN+IL-17RD+ cell, particularly as a CD45−CD31−PDPN+IL-17RD+ cell in peripheral blood.

In an embodiment, identifying and characterizing the presence of CD45−CD31−PDPN+ cells or CD45−CD31−PDPN+IL-17RD+ cells in peripheral blood provides a diagnostic which is predictive of an impending flare in an RA patient. In an embodiment, identifying and characterizing the presence of CD45−CD31−PDPN+ cells or CD45−CD31−PDPN+IL-17RD+ cells in peripheral blood provides a diagnostic which is predictive of an impending flare, or of stiffness in joints, pain throughout the body, increased difficulty doing everyday tasks, swelling, fatigue and/or flu-like symptoms in a patient, including an RA patient, or a patient which is suspected of having RA or an arthritic or inflammatory disease.

The invention thus provides a method for monitoring and predicting a rheumatoid arthritis (RA) flare or increased RA disease activity in a patient comprising:

(a) isolating a blood sample from said patient;

(b) evaluating the blood sample for expression or quantitatively increased amounts of one or more sets of antecedent RNA markers, protein markers or cell markers selected from:

-   -   (i) AC2 markers or proteins as provided in Table 7;     -   (ii) AC3 markers or proteins as provided in Table 8;     -   (iii) markers or proteins selected from COL1A2, COL5A1, COL16A1,         COL14A1, COL4A2, PXDN, ST5, DCLK1, SCARA5, EGFR, EGR1, ZFHX4,         COL3A1, COMP, FNDC1, GALNT15, SULF1, GPX8 and IGFBP6 as set out         in Table 5;     -   (iv) markers or proteins selected from COL1A2, COL5A1, COL16A1,         COL14A1, COL4A2, PXDN, ST5, DCLK1, SCARA5, EGFR, EGR1 and ZFHX4         as set out in Table 9;     -   (v) cell markers CD45− CD31−PDPN+;

(c) wherein the expression or quantitatively increased amounts of the RNA markers or proteins or

the presence of the cell markers predicts an impending RA flare.

The expression or quantitatively increased amounts of the AC2 RNA markers or proteins predicts an RA flare in about 2 weeks or about 12-14 days, with a margin of error of up to about a week or 7 days, thus in about 7-21 days. Differential expression of AC2 markers has been identified and characterized in RA patients approximately two weeks prior to the presence of symptoms indicative of an RA flare in the patients. The expression or quantitatively increased amounts of the AC3 RNA markers or proteins predicts an RA flare in about 1 week or about 5-7 days, with a margin of error of about a week or 7 days, thus in about a week or up to 2 weeks, or up to 14 days. Differential expression of AC3 markers has been identified and characterized in RA patients approximately one week or about 5-7 days prior to the presence of symptoms indicative of an RA flare in the patients. The period of time prior to recognition of flare symptoms may vary by a day, a few days or several days from either a week before or two weeks before. The variation may be as a result of the timing of blood collection or sample collection for evaluation of the marker(s). The variation may be as a result of the sensitivity of the patient to symptoms of an RA flare or the ability of a patient to identify or recognize the symptoms or any clinical parameter of a flare. In as much as physical indicators or symptoms of a flare may be selected from stiffness in joints, pain throughout the body, increased difficulty doing everyday tasks, swelling, fatigue and flu-like symptoms, these may be recognized immediately or in the short term or may be recognized after a day or two or several days of symptoms in and by a patient.

Any applicable and sufficient number of markers may be evaluated in a patient to determine or predict an impending flare. Thus, the markers should be sufficient to reliably predict an impending flare. One skilled in the art will be able to utilize the data herein and available to provide a set of markers necessary or sufficient to predict a flare. In particular and for example, markers which are associated with certain pathways or responses may be selected. Pathways involved in myeloid, neutrophil, Fc receptor signaling and platelet activation may be selected. Genes or markers associated with developmental pathways for naive B cells and leukocytes may be selected from among the AC2 genes. Naïve B cell genes may be selected from among AC2 genes. Pathways related to extracellular matrix, collagen and connective tissue development may be selected, and may be particularly selected from among the AC3 genes. The invention describes that AC3 was enriched for pathways not typical of blood samples, including cartilage morphogenesis, endochondral bone growth, and extracellular matrix organization. Genes for these pathways or associated with these may be selected from the AC3 genes as markers for predicting RA flares. AC3 is described as enriched with sublining fibroblast genes, in a particular aspect the sublining fibroblast genes CD34+, HLA-DR+, and DKK3+. AC3 is described as enriched with sublining fibroblast genes, in a particular aspect the sublining fibroblast genes CD45−CD34+, CD45− HLA-DR+, and CD45-DKK3+. In an aspect, these may be particularly selected from or included in the markers selected from the AC3 genes. In an embodiment, sublining fibroblast markers selected from the AC3 markers or proteins are selected and evaluated. In an embodiment, AC3 markers or proteins expressed by CD34+, HLADR+ and DKK3+ cells are evaluated. In an embodiment, AC3 markers or proteins expressed by CD45−CD34+, CD45-HLADR+ and CD45-DKK3+ cells are evaluated. The method includes wherein the cell marker IL17RD is also evaluated. In an embodiment, AC3 markers or proteins expressed by PRIME cells, CD45−CD31−PDPN+ cells, or CD45−CD31−PDPN+IL17RD+ cells are evaluated.

Notably, many of the relevant and most particular markers provided herein are unusual in peripheral blood and/or are not necessarily or particularly associated with inflammation or an inflammatory condition per se. This facilitates their specificity, relevance and significance in particularly or specifically predicting or implying an impending RA flare, and/or exacerbation of joint symptoms. Some prior marker studies have identified inflammatory genes, such as inflammation gene expression panels, wherein the genes are associated with RA or inflammatory type conditions of RA, such as described in U.S. Pat. No. 7,935,482. These inflammatory genes provide a distinct profile and profiling from those provided herein, are particularly skewed and relevant for inflammation, and are not predictive of an impending flare.

A subset of at least 20 of the AC2 or AC3 markers may be evaluated. In an aspect, a subset of at least 10 of the AC2 or AC3 markers are evaluated. At least 4, at least 5, at least 6, at least 7, at least 8, at least 9, at least 10, at least 11, at least 12, at least 13, at least 14, least 15, at least 16, at least 17, at least 18, at least 19, at least 20, at least 25, at least 30, at least 35, at least 40, at least 45, at least 50 of the AC2 or AC3 markers may evaluated. A subset of at least 20 of the AC2 and and at least 20 of the AC3 markers may be evaluated. In an aspect, a subset of at least 10 of the AC2 and the AC3 markers are evaluated. At least 4, at least 5, at least 6, at least 7, at least 8, at least 9, at least 10, at least 11, at least 12, at least 13, at least 14, least 15, at least 16, at least 17, at least 18, at least 19, at least 20, at least 25, at least 30, at least 35, at least 40, at least 45, at least 50 of the AC2 and the AC3 markers may evaluated.

The invention particularly relates to predicting an impending RA flare in a patient and treating for the impending flare so that the patient experiences a reduced flare, fewer pathologies and/or symptoms associated with a flare, or such that a flare and its associated disease exacerbations are reduced, limited in duration, or avoided. This a method is provided herein for predicting an impending flare and treating a flare, including thereby preventing a flare, so that prophylaxis may be achieved. This serves to significantly reduce the disease and the associated difficulties for an RA patient and provides a clinically more stable RA scenario.

Methods are provided for predicting an impending RA flare and treating a flare in a patient, including comprising:

a) isolating a blood sample from the patient;

b) contacting the blood sample with reagents specific for markers selected from a panel of RNA or protein markers to assess expression of the RNA or protein markers, wherein the panel of RNA or protein markers is selected from:

-   -   (i) AC2 markers or proteins as provided in Table 7;     -   (ii) AC3 markers or proteins as provided in Table 8;     -   (iii) markers or proteins selected from COL1A2, COL5A1, COL16A1,         COL14A1, COL4A2, PXDN, ST5, DCLK1, SCARA5, EGFR, EGR1, ZFHX4,         COL3A1, COMP, FNDC1, GALNT15, SULF1, GPX8 and IGFBP6 as set out         in Table 5;     -   (iv) markers or proteins selected from COL1A2, COL5A1, COL16A1,         COL14A1, COL4A2, PXDN, ST5, DCLK1, SCARA5, EGFR, EGR1 and ZFHX4         as set out in Table 9; and

c) comparing expression of the markers selected from a panel of RNA or protein markers in the blood sample to expression of the markers in a control blood sample to determine if expression of the markers selected from a panel of RNA or protein markers in the blood sample is increased relative to expression in the control blood sample, wherein detection of increased expression serves to predict an impending RA flare in a patient;

and treating the patient thereby diagnosed with an impending RA flare by administering a therapeutically effective amount of one or more disease modifying agent for treating RA.

The expression, differential expression, or quantitatively increased amounts of the AC2 RNA markers or proteins may predict or may be utilized to predict an RA flare in about 2 weeks, about 14 days, or about 12-14 days, up to in about 3 weeks or about 21 days, given margin of error. The expression or quantitatively increased amounts of the AC3 RNA markers or proteins may predict or may be utilized to predict an RA flare in about one week, about 7 days, or about 5-7 days, up to or about up to two weeks or about 14 days, given margin of error. In an aspect of the method, the expression, differential expression, or quantitatively increased amounts of the markers or proteins selected from COL1A2, COL5A1, COL16A1, COL14A1, COL4A2, PXDN, ST5, DCLK1, SCARA5, EGFR, EGR1, ZFHX4, COL3A1, COMP, FNDC1, GALNT15, SULF1, GPX8 and IGFBP6 or of the markers or proteins selected from COL1A2, COL5A1, COL16A1, COL14A1, COL4A2, PXDN, ST5, DCLK1, SCARA5, EGFR, EGR1 and ZFHX4 predicts an RA flare in about one week, about 7 days, or about 5-7 days, up to about two weeks or 14 days given margin of error.

Evaluation of RNA or protein expression may be conducted using any method known in the art. Thus, in accordance with the methods of the invention, RNA expression may be assessed by RT PCR. RNA expression may be determined by RNA sequencing. In accordance with the method, protein expression may be assessed using specific antibodies, assessing for protein activity, utilizing protein ligands.

Cell marker expression or presence on the surface of cells in the blood in accordance with the methods of the invention may be determined using standard and known methods. Cell markers may be evaluated using antibodies. Cell markers may be evaluated using FACs analysis. Cells or cell markers may be evaluated using cell sorting or single cell assessments. Cells, including the PRIME cells of the invention may be isolated using cell surface marker antibodies. Methods of isolating PRIME cells, characterized as CD45−CD31−PDPN+ cells, using or via cell surface markers are thus provided in an embodiment of the invention.

The disease modifying agent for treating RA may be selected from standard or clinically recognized agents or therapies for RA or arthritic conditions or inflammatory diseases and conditions. In aspects, the disease modifying agent for treating RA may be one or more agent selected from a nonsteroidal anti-inflammatory drug (NSAID), steroid, methotrexate, disease-modifying antirheumatic drug (DMARDs), biologic DMARD, and oral janus kinase (JAK) inhibitor. DMARD may be one or more of methotrexate (Trexall, Otrexup), leflunomide (Arava), hydroxychloroquine (Plaquenil) and sulfasalazine (Azulfidine). Biologic DMARD may be one or more or any of abatacept (Orencia), adalimumab (Humira), anakinra (Kineret), baricitinib (Olumiant), certolizumab (Cimzia), etanercept (Enbrel), golimumab (Simponi), infliximab (Remicade), rituximab (Rituxan), sarilumab (Kevzara), tocilizumab (Actemra) and tofacitinib (Xeljanz). Exemplary JAK inhibitor include tofacitinib (Xeljanz and Xeljanz XR), baricitinib (Olumiant), and upadacitinib (Rinvoq). The biologic DMARD may be a tumor necrosis factor (TNF) inhibitor. In an aspect, the biologic DMARD may be an anti-inflammatory antibody or an antibody directed to an inflammation or immune modulatory molecule. In an aspect, the antibody may be an interleukin antibody. The antibody may be an IL-17 specific antibody or an IL-17RD specific or IL-17RD blocking or neutralizing antibody. The antibody may be a podaplanin (PDPN) antibody. The antibody may be a bispecific podaplanin (PDPN) antibody, such as a bispecific PDPN IL17RD antibody.

A novel and unique circulating cell has been identified as a cellular indicator of an impending flare and which specifically contributes to the impending flare. Thus, a circulating pre-inflammatory mesenchymal (PRIME) cell, characterized as a CD45−CD31−PDPN+ cell, has been identified and is provided herein wherein the presence of the cell in peripheral blood is indicative or predictive of an impending RA flare. In an aspect, the PRIME cell additionally expresses IL17RD and is IL17RD+. In an aspect, a subset of PRIME cells additionally expresses IL17RD and is IL17RD+. Methods for isolating PRIME cells, CD45−CD31−PDPN+ cells, and additionally IL17RD+ cells, including for analysis and/or evaluation with potential therapeutics or cell modulators, are provided as an embodiment of the invention. The cells may be selected or isolated via their cell surface markers, including as CD45−CD31−PDPN+, additionally including IL17RD+. Methods for evaluating agents that modulate or inhibit CD45−CD31−PDPN+ cells, and additionally IL17RD+ cells, are provided.

A method is herein now provided for predicting an impending RA flare comprising evaluating a blood sample from a patient for the presence of a PRIME cell characterized as a CD45− CD31−PDPN+ cell, wherein the presence of detectable PRIME cells in peripheral blood in a patient predicts an impending RA flare in the patient. In an aspect thereof, the method includes further evaluating for the presence of IL17RD on a CD45−CD31−PDPN+ cell. Methods are provided for evaluating and treating an impending flare in an RA patient comprising evaluating the peripheral blood of a patient for the presence of a PRIME cell characterized as a CD45−CD31−PDPN+ cell and treating a patient that is positive for PRIME cells in their peripheral blood with a disease modifying agent for RA. Methods are provided for evaluating and treating an impending flare in an RA patient comprising evaluating the peripheral blood of a patient for the presence of a PRIME cell characterized as a CD45− CD31−PDPN+IL17RD+ cell and treating a patient that is positive for PRIME cells in their peripheral blood with a disease modifying agent for RA.

Methods are provided for evaluating and treating an impending flare in an RA patient comprising evaluating the peripheral blood of a patient for the presence of RNA(s) or protein(s) expressed, specifically expressed or particularly expressed by a PRIME cell characterized as a CD45− CD31−PDPN+ cell and treating a patient that is positive for expressing, specifically expressing or particularly expressing RNA(s) or protein(s) of PRIME cells in their peripheral blood with a disease modifying agent for RA. Methods are provided for evaluating and treating an impending flare in an RA patient comprising evaluating the peripheral blood of a patient for the presence of RNA(s) or protein(s) expressed, specifically expressed or particularly expressed by a cell characterized as a CD45−CD31−PDPN+IL17RD+ cell and treating a patient that is positive for the presence of RNA(s) or protein(s) expressed, specifically expressed or particularly expressed by a cell characterized as a CD45−CD31−PDPN+IL17RD+ cell in their peripheral blood with a disease modifying agent for RA. The specification details the overlapping expression of various and numerous specific AC3 marker genes with gene expression (for example as detected by RNA presence) in PRIME cells characterized as a CD45−CD31−PDPN+ cells.

The disease modifying agent may be selected from those as described and provided herein or as known and recognized to a clinician or physician. Antibodies directed to immune modulators or inflammatory modulators may be selected. In an aspect, the patient is treated with an IL-17 or IL-17RD antibody. In another aspect, the patient is further treated with an anti-inflammatory agent and/or an immune modulating agent. In an aspect the patient is treated with a podaplanin (PDPN) antibody. In an aspect the patient is treated with one or more antibody directed to a surface marker on the PRIME cell, for example a marker from among the AC3 gene markers which is expressed on the cell surface. In an aspect the patient is treated with one or more antibody directed to a surface marker selected from the markers or proteins COL1A2, COL5A1, COL16A1, COL14A1, COL4A2, PXDN, ST5, DCLK1, SCARA5, EGFR, EGR1, ZFHX4, COL3A1, COMP, FNDC1, GALNT15, SULF1, GPX8 and IGFBP6.

Two monoclonal antibodies targeting IL-17A (Secukinumab (AIN457, Novartis), Ixekizumab (LY2439821, EliLilly) and one against the IL-17 receptor (Brodalumab (KHK4827, AMG827, Kyowa/Amgen) are approved for the treatment of moderate-to-severe plaque psoriasis (Silfvast-Kaiser A et al (2019) Expert Opin Biol Ther 19(1):45-54; doi: 10.1080/14712598.2019.1555235). Other IL-17A antibodies include Remtolumab (ABT-122, Abbvie), ALX-0761 (MSB0010841, Ablynx/Merck), BCD-085 (Biocad), COVA322 (Covagen), LY3114062 (EliLilly), Perakizumab (RG4934, RO5310074, Hoffman-LaRoche), Vunakizumab (SHR-1314, Jiangsu Hengrui), CNTO 6785 (Morphosys/Janssen), CJM112 (Novartis) and Bimekizumab (UCB4940, UCB) (Ibrahim S et al (2017) Clin Colorectal Cancer 17(1):e109-13). The IL-17A specific antibody secukinumab and other anti-IL-17 agents have also been reported effective in ankylosing spondylitis (Wendling D et al (2019) Expert Opin Biol Ther 19(1):55-64. doi: 10.1080/14712598.2019.1554053). These antibodies are of use and application in accordance with the invention.

Podaplanin (PDPN) antibodies have also been described. These include the anti-podaplanin antibody clone 8.1.1 (Lax S et al (2017) BMJ Open Respiratory Res 4:e000257.doi:10.11361/bmjresp-2017-000257), a chimeric mouse-human podaplanin anibody chLpMab-7 (Kato Y (2015) Oncotarget 6(34):36003-36018) and anti-human podaplanin rat antibody NZ-1 and chimeric rat-human antibody derived therefrom (NZ-8) Abe S et al (2013) J Immunol 190(12):6239-6249).

Immune modulators may be included in a composition with or administered with antibodies or agents, including those targeting the markers or proteins of the invention, and/or administered at a different time to enhance immune modulation and/or RA therapy, including immune therapies directed against RA or RA flares. An immune modulator may be an adjuvant. Applicable immune modulators include IDO, TDO (Platten M (2012) Cancer Research 72(21):5435-40), □-galactosyl ceramide and analogs thereof such as threitolceramide (ThrCer) and ThrCer 6, TLR ligands such as poly I:C (TLR3), MPL (TLR4), imiquimod (TLR7), R848 (TLR8) or CpG (TLR9), iCOS, CTLA-4, PD1, PD1 ligand, OX40 and OX40 ligand, Lag3, GITR, GITR ligand interleukins, tumor necrosis factor (TNF) or other growth factors, colony stimulating factors, T cell modulators including modulators of CD8⁺ T cells, cytokines or hormones which stimulate the immune response or reduction or elimination of cancer cells or tumors (Mellman I (2011) Nature (480):480-489). Additional immunmodulators are small molecules, antagonist antibodies or agonist antibodies targeting the applicable immune modulators including IDO, TDO, Toll like receptor family or iCOS, CTLA-4, PD1, PD1 ligand, OX40 and OX40 ligand, interleukins, tumor necrosis factor (TNF) or other growth factors, colony stimulating factors, T cell modulators including modulators of CD8⁺ T cells, cytokines which stimulate the immune response or reduction or elimination of cancer cells or tumors. Additional immune modulators, including TLR ligands such as poly I:C (TLR3), MPL (TLR4), imiquimod (TLR7), R848 (TLR8) or CpG (TLR9) can be used, including in combination with other modulators, agents or antibodies.

The unique specificity of the markers of the invention provides diagnostic and therapeutic uses to identify, characterize and target RA flares or conditions and symptoms associated with an arthritis and/or inflammatory condition, particularly prior to the appearance of clinical symptoms. In particular, markers of the invention are useful in modulating arthritic or inflammatory disease, particularly RA. Markers of the invention are useful in inflammatory arthritis associated disorders, particularly rheumatoid arthritis (RA). Markers may further be useful in other conditions of inflammatory arthritis, particularly psoriatic arthritis (PsA), systemic lupus erythematosus (SLE, lupus), ankylosing spondylitis (AS), and gouty arthritis (gout). In an aspect thereof, antibodies or agents targeting the RNA markers or protein markes are useful in modulating an RA flare or joint inflammation or other physical indicators and symptoms of an RA flare. The antibodies or agents have applicability in therapeutic treatment or management of RA. The antibodies or agents may further have applicability in other common inflammatory arthritis associated disorders, particularly and such as psoriatic arthritis (PsA), systemic lupus erythematosus (SLE, lupus), ankylosing spondylitis (AS), and gouty arthritis (gout). The antibodies or agents targeting the RNA markers or proteins have applicability in enhancing the therapeutic effect including the anti-rheumatic effect of traditional RA disease modifying agents or therapy(ies).

The invention includes a set of RNA or protein markers for evaluating and predicting an impending RA flare in a patient comprising the markers selected from:

(i) a subset of at least 20 markers from the AC2 markers provided in Table 7;

(ii) a subset of at least 20 markers from the AC3 markers provided in Table 8;

(iii) markers selected from COL1A2, COL5A1, COL16A1, COL14A1, COL4A2, PXDN, ST5, DCLK1, SCARA5, EGFR, EGR1, ZFHX4, COL3A1, COMP, FNDC1, GALNT15, SULF1, GPX8 and IGFBP6 as set out in Table 5;

(iv) markers selected from COL1A2, COL5A1, COL16A1, COL14A1, COL4A2, PXDN, ST5, DCLK1, SCARA5, EGFR, EGR1 and ZFHX4 as set out in Table 9.

The markers may be a subset of at least 20 of the AC2 or AC3 markes, a subset of at least 10 of the AC2 or AC3 markers. At least 4, at least 5, at least 6, at least 7, at least 8, at least 9, at least 10, at least 11, at least 12, at least 13, at least 14, least 15, at least 16, at least 17, at least 18, at least 19, at least 20, at least 25, at least 30, at least 35, at least 40, at least 45, at least 50 of the AC2 or AC3 markers may be included. Particular markers may be selected and utilized. An AC2 marker subset may comprise naïve B cell gene markers and markers of developmental pathways for naïve B cells and leukocytes. A subset of AC3 markers may comprise markers of cartilage morphogenesis, endochondral bone growth, extracellular matrix organization and sublining fibroblasts. A subset of AC3 markers may comprise markers which are expressed or differentially expressed by PRIME cells, CD45−CD31−PDPN+ or are CD45−CD31−PDPN+IL17RD+ cells, cells precursors to sublining fibroblasts, particularly RA sublining fibroblasts.

The set of markers provided and/or utilized in accordance with the methods hereof may be one or more markers selected from COL1A2, COL5A1, COL16A1, COL14A1, COL4A2, PXDN, ST5, DCLK1, SCARA5, EGFR, EGR1, ZFHX4, COL3A1, COMP, FNDC1, GALNT15, SULF1, GPX8 and IGFBP6. In an aspect, a set of one or more markers selected from COL1A2, COL5A1, COL16A1, COL14A1, COL4A2, PXDN, ST5, DCLK1, SCARA5, EGFR, EGR1 and ZFHX4 is provided and/or utilized in accordance with the methods hereof. A set of, or one or more sets of, two or more, three or more, four or more, five or more, six or more, seven or more, eight or more, nine or more, ten or more, a dozen, at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least ten, a set of 5-10, a set of 3-5, a set of 5-7, a set of 3-7, a set of 5-8 selected from COL1A2, COL5A1, COL16A1, COL14A1, COL4A2, PXDN, ST5, DCLK1, SCARA5, EGFR, EGR1, ZFHX4, COL3A1, COMP, FNDC1, GALNT15, SULF1, GPX8 and IGFBP6 is provided and/or utilized in accordance with the methods hereof. A set of, or one or more sets of, two or more, three or more, four or more, five or more, six or more, seven or more, eight or more, nine or more, ten or more, a dozen, at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least ten, a set of 5-10, a set of 3-5, a set of 5-7, a set of 3-7, a set of 5-8 selected from COL1A2, COL5A1, COL16A1, COL14A1, COL4A2, PXDN, ST5, DCLK1, SCARA5, EGFR, EGR1 and ZFHX4 is provided and/or utilized in accordance with the methods hereof. Multiple sets may be utilized, for example a set of markers of one type or metabolic pathway, combined with a distinct set of another type or metabolic or cellular pathway or cell.

The present invention also relates to a variety of diagnostic applications, including methods for detecting the expression of or elevated presence of any of the makers of the invention, particularly the RNA markers or protein markers described and provided herein. Thus, the presence or amount of RNA or protein is evaluated. Protein may be evaluated by reference to their ability to be recognized by a specific antibody directed thereto. Peptide complexes can be identified, targeted, labeled, and/or quantitated on cells, including cell(s) in peripheral blood. Diagnostic applications include in vitro and in vivo applications well known and standard to the skilled artisan and based on the present description. Diagnostic assays and kits for in vitro assessment and evaluation of marker status or marker amounts may be utilized to diagnose, evaluate and monitor patient samples including those known to have or suspected of having arthritis, inflammatory arthritis, or RA. The assessment and evaluation of RA disease status is useful in determining the suitability of a patient for a clinical trial of a drug or for the administration of a particular therapy or disease modifying agent, including a DMARD or an antibody, including as described herein, including combinations thereof, versus a different agent or therapy. This type of diagnostic monitoring and assessment is already in practice utilizing antibodies against the HER2 protein in breast cancer (Hercep Test, Dako Corporation), where the assay is also used to evaluate patients for antibody therapy using Herceptin. In vivo applications may include imaging of joints, including radioimaging.

In a further embodiment, commercial test kits suitable for use by a medical specialist may be prepared to determine the presence or absence of aberrant, differential or increased expression of one or more or of a subset of markers described herein. One class of kits will contain at least the labeled marker or its binding partner, for instance an antibody specific thereto, and directions, of course, depending upon the method selected. The kits may also contain peripheral reagents such as buffers, stabilizers, etc.

Accordingly, a test kit may be prepared for the demonstration of the presence of or elevated levels of one or more marker or protein marker of an impending RA flare, comprising:

(a) a predetermined amount of at least one labeled immunochemically reactive component obtained by the direct or indirect attachment of the protein marker or a specific binding partner or antibody thereto, to a detectable label;

(b) other reagents; and

(c) directions for use of said kit. In accordance with the above, an assay system for screening potential drugs effective to modulate an RA flare or prevent an RA flare and/or the activity of a marker or protein marker of the present invention may be prepared. The marker peptide or antibody thereto may be introduced into a test system, and the prospective drug may also be introduced into the resulting system cell culture, and the culture thereafter examined to observe any changes in the activity of the cells, binding of the antibody, or amount and extent of the marker due either to the addition of the prospective drug alone, or due to the effect of added quantities of a known agent(s).

The invention provides a system or kit for predicting an impending RA flare comprising a set of markers as described and provided herein or a set of probes and/or antibodies for evaluating a set of markers as described and provided herein.

As an example, a kit or system may include a set of markers or a set of probes and/or antibodies for evaluating a set of markers selected from or for a or any combination of:

(i) a subset of at least 20 markers from the AC2 markers provided in Table 7;

(ii) a subset of at least 20 markers from the AC3 markers provided in Table 8;

(iii) markers selected from COL1A2, COL5A1, COL16A1, COL14A1, COL4A2, PXDN, ST5, DCLK1, SCARA5, EGFR, EGR1, ZFHX4, COL3A1, COMP, FNDC1, GALNT15, SULF1, GPX8 and IGFBP6 as set out in Table 5;

(iv) markers selected from COL1A2, COL5A1, COL16A1, COL14A1, COL4A2, PXDN, ST5, DCLK1, SCARA5, EGFR, EGR1 and ZFHX4 as set out in Table 9.

The system or kit may further comprise a means for collection of the patient's blood by fingerstick.

The invention may be better understood by reference to the following non-limiting Examples, which are provided as exemplary of the invention. The following examples are presented in order to more fully illustrate the preferred embodiments of the invention and should in no way be construed, however, as limiting the broad scope of the invention.

Example 1 Longitudinal Genomics Identifies PRIME Cells as Antecedents of Rheumatoid Arthritis Flares

Rheumatoid arthritis (RA), like many inflammatory diseases, is characterized by episodes of quiescence and exacerbation (flares). The molecular events leading to flares are unknown. We established a clinical and technical protocol for repeated home blood collection in RA patients to allow for longitudinal RNA sequencing (RNAseq). Samples were obtained from 364 time points from eight flares over four years in our index patient, and 235 time points from flares in three additional patients. We identified transcripts that were differentially expressed antecedent to flares and compared these to synovial single cell RNAseq (scRNAseq). Flow cytometry and sorted blood cell RNAseq in additional RA patients were used to validate the findings.

Consistent changes were observed in blood transcriptional profiles one to two weeks antecedent to RA flare. B cell activation was followed by expansion of a previously unexplored circulating CD45−/CD31−/PDPN+, PRe-Inflammatory MEsenchymal (“PRIME”) cell in RA patient blood, which shared features of inflammatory synovial fibroblasts. Circulating PRIME cells decreased during flares from all four patients, and flow cytometry and sorted cell RNAseq confirmed the presence of PRIME cells in 19 additional RA patients.

Longitudinal genomic analysis of RA flares reveals PRIME cells in RA blood, and suggests a model in which they become activated by B cells in the weeks prior to RA flare, and then migrate out of the blood to the synovium. Longitudinal RNAseq analysis can be used to reveal dynamic changes leading to flares of chronic inflammatory disease.

Rheumatoid arthritis (RA) symptoms are highly dynamic, with stable periods interrupted by unpredictable flares of disease activity. Such waxing/waning clinical courses are characteristic of many autoimmune diseases, including multiple sclerosis (1), systemic lupus erythematosus (2), and inflammatory bowel disease (3,4), underscoring a need to develop approaches to understand what triggers transitions from quiescence to flare in autoimmune disease.

This study explores disease pathophysiology with a longitudinal, prospective analysis of blood transcriptional profiles in individual RA patients over time. Previous microarray studies of RA blood samples from relatively sparse time series data have identified few significant gene changes associated with disease activity (5-8). Here we provide the first RA study to look for molecular changes in blood that anticipate clinical flares. To do so we optimized methods by which RA patients themselves could collect high quality finger stick blood samples for RNA sequencing (RNAseq), facilitating weekly blood sampling for months to years.

We analyzed patient reports of clinical disease activity and RNAseq data from four patients across multiple clinical flares. In our most deeply studied index case, we assessed 364 time points by RAPID3 from eight flares over four years, and analyzed 84 time points assessed by RNAseq. Collecting samples longitudinally enabled a search for transcriptional signatures that preceded clinical symptoms.

Comparing these blood RNA profiles to synovial single cell RNAseq (scRNAseq) data (9) provided evidence that a biologically coherent set of transcripts are significantly increased in the blood prior to symptom onset, and a subset of these decrease as the patients begin to experience symptoms. These latter transcripts overlap with and likely demarcate cellular precursors to a novel subset of synovial sublining fibroblast cell types detected in inflamed RA synovium using scRNAseq. Analysis in 19 additional RA patients corroborated our findings. Our data suggests a model in which a previously unexplored circulating mesenchymal cell type, detectable in the weeks prior to RA flare, becomes activated by B cells and subsequently leaves the blood, traffics to synovium, and contributes to disease activity.

Methods

Patient Data

All patients met American College of Rheumatology/European League Against Rheumatism 2010 (10,11) criteria for RA and were seropositive for cyclized citrullinated protein antibody (CCP). Disease activity was assessed from home each week, or up to 4 times daily during escalation of flares, using the routine assessment of patient index data 3 (RAPID3) questionnaire (12). Disease activity was also assessed at clinic visits, each month, and during flares, using both the RAPID3 and the disease activity score 28 (DAS28), which incorporates tenderness and swelling from 28 joints, erythrocyte sedimentation rate (ESR) and patient global assessment of disease activity. Complete blood counts (CBC) including white blood cells (WBC), neutrophils, monocytes, lymphocytes, and platelets were performed by the clinical lab at Memorial Sloan Kettering Cancer Center. We collected 43 clinic visits from the index patient, and 25, 14 and 12 clinic visits for the other three patients studied longitudinally. Nineteen additional seropositive RA patients and 18 age and sex matched non-RA patients, for whom peripheral blood mononuclear cells (PBMC) were available, were also studied for the presence of PRIME cells by FACS and RNAseq analysis.

RNA Preparation from Finger Stick Blood

Patients self-performed finger sticks at home to collect three drops of blood into a microtainer tube prefilled with fixative, and samples were mailed overnight each week. RNA was extracted using the PAXgene RNA kit and purified per manufacturer's protocols, except the volume of all washes and elutions was decreased to 25% of the recommended volume by the manufacturer. RNA was assessed using the Agilent BioAnalyzer for quantity and quality. For library preparation, we used the GlobinZero kit (EpiCentre #GZG1224) and Illumina's Truseq mRNA Stranded Library kit, with 11-12 PCR cycles for 5-8 nM input and sequenced on HiSeq2500 with 150 base paired-end reads. Reads were aligned to Gencodev18 using STAR and quantified using featureCounts (v1.5.0-p2). Samples with at least four million paired-end reads were retained for analysis.

Data Analysis:

Comparison of Disease Activity Measures

To describe the bivariate relationship of disease activity with RAPID3, we used the locally weighted scatterplot smoothing (LOWESS) technique. R² were calculated to assess correlations of CBC counts inferred from CIBERSORTx and counts measured by clinical labs. Inferred CIBERSORTx lymphocyte counts were the sum of B cells naive+B cells memory+T cells CD8+T cells CD4 naive+T cells CD4 memory resting+T cells CD4 memory activated. Monocytes, Macrophages M0, Macrophages M1, and Macrophages M2 were summed to infer CIBERSORTx monocyte counts. One-way ANOVA was used to test for significant differences among various clinical features according to disease activity state.

Differential Expression Analyses Across Patients

Samples were labeled “baseline” (stable RAPID3), “flare” (RAPID3 scores rose over two standard deviations above the baseline mean), or “steroid”. EdgeR (v3.24.3) (13) was used to analyze flare vs baseline differential gene expression. Permutation test (n=1 ×106) was used to test for the significance of overlap between genes decreased in flares in the index patient and patients 2, 3, and 4. GO enrichment (goana, from limma v3.38.3) (14) was used to identify enriched pathways in significantly differentially expressed genes in the index patient (FDR<0.1) and consistent in the direction of expression in both the index and replication patients (i.e., log fold change either both positive or both negative).

Time Series Analysis of Index Patient

We performed longitudinal data analysis on the index patient using ImpulseDE2 (v1.8.0) (15). Flare onset was defined clinically (as above) and samples from 8 weeks prior to flare up to 4 weeks after flare were analyzed (excluding any samples during which the patient was taking steroids, n=65 samples). The date of library preparation was included in the model for batch correction, and the genefilter (v1.64.0) package (16) was used to filter out lowly expressed genes.

Identification and Characterization of Coexpressed Gene Modules

We hierarchically clustered mean expression of significantly differentially expressed genes identified in the ImpulseDE2 analysis by week to flare initiation (batch corrected logrpkm expression values were calculated using edgeR) and identified five coexpressed gene modules (Clusters 1-5). We analyzed these five modules for GO term enrichment (goana).

To compare differentially expressed gene modules and to further characterize expression patterns in gene modules over time, for each module, the mean expression level for each gene was calculated across flares per week, then normalized across weeks. ABIS (17) and CIBERSORTx (18) were used to deconvolute gene expression data. To aggregate a given cluster of genes or cell type with gene markers, the mean of standardized gene expression scores or deconvolved cell type scores, respectively, within each week were plotted. To identify synovial scRNAseq cluster specific marker gene signatures, we used a previously published dataset (18) to compare the cells from one scRNAseq cluster with cells from all the other scRNAseq clusters using the single-cell RNA-seq log 2(CPM+1) matrix. We generated lists of the top 200 marker genes for each cluster using the criteria of 1) log 2FC greater than 1, 2) auc greater than 0.6, and 3) percent of expressing cells greater than 0.4. We used Fisher's exact test to evaluate enrichment of synovial cell subtype marker genes in the 5 coexpressed gene modules. P-values were corrected for multiple hypothesis test correction using the Benjamini-Hochberg procedure.

Flow Cytometry and Sorting

To assess percentages of PRIME cells in peripheral blood mononuclear cells, samples from PBMC were stained with antibodies to: CD31-APC, (WM59), Mouse IgG1-APC (MOPC-21), PDPN-PerCP (NZ1.3), Rat IgG2a (eBR2a)-PerCP, CD45-PE (H130), Mouse IgG1-PE (MOPC-21) and TO-PRO®-3 and analyzed on BD-FACSCalibur using FlowJo 10.6.1. To flow sort and sequence PRIME cells, 20-100 Million cells from CD14-depleted leukapheresates were stained with CD31−APC(WM59), Mouse IgG1-APC(MOPC-21), PDPN-PerCP(NZ1.3), Rat IgG2a-PerCP(eBR2a), CD45−FITC(HI30), Mouse IgG1-FITC(MOPC-21), and DAPI (4′, 6-Diamidino-2-Phenylindole, Dihydrochloride) and sorted on a BD FACSAria II. Illumina Stranded TruSeq library kit was used to generate cDNA libraries that were sequenced on MiSeq. DESeq2 (v1.24.0) (19) was used for differential expression analysis.

Statistics

R2 and Pearson correlation coefficients were calculated to assess the bivariate linear fit of disease activity measured by RAPID3 and DAS28 as well as CBC counts inferred from CIBERSORT cell counts and counts measured by clinical labs. Inferred CIBERSORTx lymphocyte counts were the sum of B cells naive+B cells memory+T cells CD8+T cells CD4 naive+T cells CD4 memory resting+T cells CD4 memory activated. One way ANOVA was used to test for significant differences among various clinical features according to disease activity state. Monocytes, Macrophages M0, Macrophages M1, and Macrophages M2 were summed to infer CIBERSORTx monocytes.

Results

Clinical Protocol Development

We developed strategies for home blood collection that would allow high quality and quantity RNA for sequencing (FIGS. 6-12 ; 15-50 ng RNA; RNA integrity (RIN) scores (mean 6.9+/−standard deviation 1.7). Study patients also documented disease activity (RAPID3 questionnaires). Four RA patients were followed for one to four years with weekly home collection of finger stick blood samples coupled with completion of RAPID3 and monthly clinic visits, where DAS28 were collected (FIG. 1A). RNA was sequenced from a total of 189 finger stick blood samples from 4 patients, of which 162 (87%) passed quality control filtering.

To assess the validity of patient reported disease activity, we compared their RAPID3 scores with clinician collected DAS28. Significant correlations were evident between RAPID3 and DAS28 for each of the four patients (FIG. 1B and FIG. 13 ). To assess the validity of fingerstick blood data, we compared RNAseq inferred white blood cell counts with clinical laboratory measurements of complete blood counts and again observed significant correlations (FIG. 1C), suggesting RNAseq of finger stick blood was of sufficient quality to provide information that correlated with gold standard clinical measurements of blood counts. Taken together, these data indicate that patient reports of disease activity paired with fingerstick blood samples provide a high quality and robust means by which individuals can participate in longitudinal clinical research studies.

Clinical and Molecular Features of RA Flare Compared to Baseline

Flares were associated with increases in objective clinical and laboratory measures of RA related disease activity in the index patient (FIG. 2A and FIG. 14 ). Fingerstick RNAseq identified 2613 genes differentially expressed at flare versus baseline (FDR<0.1), with 1437 increased during flare (log FC>0; FIG. 2B and Table 1).

TABLE 1

-   -   Genes differentially expressed at flare vs baseline FDR<0.1 2613         genes     -   Genes increased during flare log FC>0 1437 genes

Pathway analysis identified enrichment in myeloid, neutrophil, Fc receptor signaling and platelet activation (FIG. 2C and Table 2), consistent with clinical blood count measurements during flares (FIG. 14 ). Interestingly, 1176 genes were significantly decreased during flare, and pathway analysis of these genes were enriched for extracellular matrix, collagen and connective tissue development (FIG. 2D and Table 2).

Time Series Analysis of Molecular Events Leading to RA Flares

To analyze the trajectories of gene expression over time and identify potential antecedents to flare, we performed time series analysis of the RNAseq data (FIG. 3A). Notably, disease activity scores in the weeks just prior to flare were the same as baseline scores two months prior to flare, underscoring the challenges of identifying both a time frame and gene expression signature that is antecedent to flare. We focused the analysis on 65 samples acquired 8 weeks prior to flare and 4 weeks after flare initiation, binning samples according to the week they were drawn. This identified 2791 genes with significant differential expression over time to flare (FDR<0.05), and hierarchical clustering of gene expression identified five clusters (FIG. 3B and Table 3).

TABLE 3 Differentially Expressed Genes

-   -   27,775 genes analyzed 2,791 genes with significant differential         expression over time to flare (FDR<0.5)

Cluster 1 represented a group of genes which increased after symptom onset (FIGS. 3C and D) and was highly overlapping (FIG. 3E) with genes increased in the flare versus baseline analysis (FIG. 2B). These gene expression clusters were reproducibly altered in 5 separate clinical flare events (FIG. 15 ).

We further focused on two clusters that were differentially expressed antecedent to flare (FIG. 3C-D). Antecedent cluster 2 (AC2) transcripts increased two weeks prior to flare and were enriched with developmental pathways for naive B cells and leukocytes. Two additional means of deconvoluting the RNAseq data, CIBERSORTx and ABIS, independently confirmed evidence of B cell and T cell populations antecedent to flare, and all analyses showed evidence of innate inflammatory signatures (neutrophils and monocytes) during flare (FIGS. 16-17 ).

Antecedent cluster 3 (AC3) transcripts increased the week prior to flare and then decreased for the duration of flare (FIGS. 3C and D). AC3 was enriched for pathways not typical of blood samples, including cartilage morphogenesis, endochondral bone growth, and extracellular matrix organization (FIG. 3E and Table 4), suggesting the presence of an uncharacterized cell type, a mesenchymal cell.

TABLE 4 go.id Term N fdr.DE1 fdr.DE2 fdr.DE3 fdr.DE4 fdr.DE5 GO:0032501 multicellular 7510 0.33779658 0.996446813 1.90E−13 0.18155513 0.996446813 organismal process GO:0009887 animal organ 982 1 1 2.60E−09 0.426866243 1 morphogenesis GO:0009653 anatomical structure 2604 0.017009962 0.739725387 3.66E−08 0.089707123 0.890858017 morphogenesis GO:0048468 cell development 2093 0.325922506 0.824909599 4.99E−08 0.826157616 1 GO:0007275 multicellular organism 5330 0.646941518 0.106039186 4.42E−07 0.016979265 0.129190893 development GO:0048856 anatomical structure 5810 0.111685048 0.184216961 5.65E−07 0.026184522 0.332210519 development GO:0030154 cell differentiation 4100 0.314553949 0.088217999 6.95E−07 0.437802459 0.771708045 GO:0032502 developmental process 6212 0.143287026 0.135556704 7.02E−07 0.017411509 0.228640051 GO:0007399 nervous system 2296 0.818972317 0.660623511 1.57E−06 0.179563884 1 development GO:0043269 regulation of ion 660 1 1 1.82E−06 1 1 transport GO:0048869 cellular developmental 4282 0.131591479 0.07488625 3.00E−06 0.474081007 0.996446813 process GO:0060536 cartilage 29 1 1 3.34E−06 1 1 morphogenesis GO:0048731 system development 4783 0.739725387 0.088328136 3.53E−06 0.025908171 0.266607283 GO:0034220 ion transmembrane 1122 1 1 3.55E−06 1 1 transport GO:0048729 tissue morphogenesis 612 0.996446813 1 6.32E−06 1 1 GO:0006811 ion transport 1638 1 1 6.53E−06 1 1 GO:0006812 cation transport 1128 1 1 9.04E−06 1 1 GO:0098660 inorganic ion 824 1 1 9.45E−06 1 1 transmembrane transport GO:0003008 system process 2148 1 1 9.57E−06 1 1 GO:0034765 regulation of ion 454 1 1 1.87E−05 1 1 transmembrane transport GO:0003414 chondrocyte 18 1 1 1.93E−05 1 1 morphogenesis involved in endochondral bone morphogenesis GO:0003429 growth plate cartilage 18 1 1 1.93E−05 1 1 chondrocyte morphogenesis GO:0090171 chondrocyte 18 1 1 1.93E−05 1 1 morphogenesis GO:0030001 metal ion transport 858 0.616825534 1 2.52E−05 1 1 GO:0003422 growth plate cartilage 19 1 1 2.83E−05 1 1 morphogenesis GO:0022008 neurogenesis 1555 0.665596251 1 3.83E−05 0.139859641 1 GO:0007155 cell adhesion 1390 0.001076518 1 4.21E−05 0.598967854 1 GO:0048699 generation of neurons 1459 0.650883021 1 4.35E−05 0.280105182 1 GO:0022610 biological adhesion 1398 0.001270754 1 5.07E−05 0.445725934 1 GO:0034762 regulation of 535 1 1 5.53E−05 1 1 transmembrane transport GO:0055085 transmembrane 1514 1 1 6.85E−05 1 1 transport GO:0030182 neuron differentiation 1317 0.768500111 1 7.84E−05 0.415235372 1 GO:0003416 endochondral bone 43 1 1 8.11E−05 1 1 growth GO:0003433 chondrocyte 23 1 1 0.000111249 1 1 development involved in endochondral bone morphogenesis GO:0098868 bone growth 45 1 1 0.000118729 1 1 GO:0032989 cellular component 1079 0.019925787 0.99915203 0.000144687 0.890858017 0.757703978 morphogenesis GO:0003418 growth plate cartilage 24 1 1 0.000151713 1 1 chondrocyte differentiation GO:0003417 growth plate cartilage 36 1 1 0.000217688 1 1 development GO:0007268 chemical synaptic 690 0.480223653 1 0.000225474 0.324979313 1 transmission GO:0098916 anterograde trans- 690 0.480223653 1 0.000225474 0.324979313 1 synaptic signaling GO:0006814 sodium ion transport 215 1 1 0.00025748 1 1 GO:0099537 trans-synaptic 698 0.517697406 1 0.000288644 0.347784599 1 signaling GO:0099536 synaptic signaling 703 0.275739603 1 0.000337001 0.357514166 1 GO:0009888 tissue development 1961 1 1 0.000413598 1 1 GO:0050954 sensory perception of 161 1 1 0.000527109 1 1 mechanical stimulus GO:0003413 chondrocyte 29 1 1 0.000545066 1 1 differentiation involved in endochondral bone morphogenesis GO:0007605 sensory perception of 142 1 1 0.000581084 1 1 sound GO:0032879 regulation of 2746 4.21E−05 1 0.000674069 1 1 localization GO:0060350 endochondral bone 71 1 0.901231612 0.000675474 1 1 morphogenesis GO:0098655 cation transmembrane 827 1 1 0.00080515 1 1 transport GO:2001223 negative regulation of 12 1 1 0.00080515 1 1 neuron migration GO:0000904 cell morphogenesis 712 0.890858017 0.965146807 0.001032945 0.616825534 0.410213141 involved in differentiation GO:0002063 chondrocyte 45 1 1 0.001076518 1 1 development GO:0048513 animal organ 3455 1 0.063098951 0.00108333 0.745168516 0.665596251 development GO:0060349 bone morphogenesis 111 1 0.469843251 0.00108657 1 1 GO:0060351 cartilage development 46 1 1 0.001251135 1 1 involved in endochondral bone morphogenesis GO:0000902 cell morphogenesis 980 0.022949891 1 0.001401799 0.797071186 0.796314167 GO:0007267 cell-cell signaling 1584 0.543286651 1 0.001964875 0.171334526 1 GO:0015672 monovalent inorganic 526 1 1 0.002079582 1 1 cation transport GO:0098662 inorganic cation 739 1 1 0.002079582 1 1 transmembrane transport GO:0044703 multi-organism 1004 1 1 0.002354643 1 1 reproductive process GO:0048666 neuron development 1071 0.745168516 1 0.002354643 0.489378401 1 GO:0042391 regulation of 424 1 1 0.003216776 0.716801532 1 membrane potential GO:0006936 muscle contraction 351 0.357514166 1 0.004649326 1 1 GO:0048589 developmental growth 646 1 1 0.004771785 1 1 GO:0051049 regulation of transport 1806 0.0059057 1 0.006500421 1 1 GO:1904062 regulation of cation 314 1 1 0.008881305 1 1 transmembrane transport GO:0048705 skeletal system 236 1 1 0.009182742 0.996446813 1 morphogenesis GO:0032412 regulation of ion 238 1 1 0.009921143 1 1 transmembrane transporter activity GO:0031175 neuron projection 941 0.594734994 1 0.010301477 0.317513419 1 development GO:0007389 pattern specification 434 1 1 0.011108198 1 1 process GO:0030198 extracellular matrix 348 1 1 0.011108198 1 1 organization GO:0098656 anion transmembrane 268 1 1 0.011788736 1 1 transport GO:0048812 neuron projection 621 1 1 0.012239952 0.507490051 0.717048855 morphogenesis GO:0032990 cell part 655 1 1 0.01290706 0.646941518 0.802166171 morphogenesis GO:0022898 regulation of 245 1 1 0.013282485 1 1 transmembrane transporter activity GO:0007160 cell-matrix adhesion 222 0.005606843 1 0.014820961 1 1 GO:0022414 reproductive process 1423 1 1 0.015397049 1 1 GO:0072025 distal convoluted 5 1 1 0.015849029 1 1 tubule development GO:0072221 metanephric distal 5 1 1 0.015849029 1 1 convoluted tubule development GO:0000003 reproduction 1426 1 1 0.015996351 1 1 GO:0002009 morphogenesis of an 479 1 1 0.016789679 1 1 epithelium GO:0120039 plasma membrane 635 1 1 0.016801155 0.56362124 0.745168516 bounded cell projection morphogenesis GO:0048858 cell projection 636 1 1 0.017059196 0.568448591 0.745168516 morphogenesis GO:0017156 calcium ion regulated 153 1 0.996446813 0.017665674 1 1 exocytosis GO:0098661 inorganic anion 110 1 1 0.019146167 1 1 transmembrane transport GO:0007215 glutamate receptor 90 1 1 0.019925787 0.665596251 1 signaling pathway GO:0035249 synaptic transmission, 90 1 1 0.019925787 1 1 glutamatergic GO:0050877 nervous system 1406 1 1 0.019979972 1 1 process GO:0003012 muscle system process 456 0.371617002 1 0.020005602 1 1 GO:1901018 positive regulation of 24 1 1 0.020370955 1 1 potassium ion transmembrane transporter activity GO:0060429 epithelium 1227 1 1 0.020590857 1 1 development central nervous system development GO:0007417 948 1 0.996446813 0.021561593 0.922242032 1 GO:0051216 cartilage development 206 1 1 0.021561593 0.78080559 1 GO:0019226 transmission of nerve 72 1 1 0.022053268 1 1 impulse GO:0051179 localization 6555 4.55E−10 1 0.022789146 0.56362124 1 GO:0032409 regulation of 260 1 1 0.022963874 1 1 transporter activity GO:0060348 bone development 208 1 0.489378401 0.023314211 1 1 GO:0030048 actin filament-based 136 1 1 0.023984508 1 1 movement GO:0030049 muscle filament 39 1 1 0.024126389 1 1 sliding GO:0033275 actin-myosin filament 39 1 1 0.024126389 1 1 sliding GO:0070252 actin-mediated cell 114 1 1 0.024126389 1 1 contraction GO:2001222 regulation of neuron 39 1 1 0.024126389 1 1 migration GO:0061448 connective tissue 263 1 1 0.02536056 0.219616377 1 development GO:2001257 regulation of cation 162 1 1 0.026700112 1 1 channel activity GO:0007423 sensory organ 532 1 1 0.027749721 1 1 development GO:0002062 chondrocyte 117 1 1 0.0280421 1 1 differentiation GO:0044057 regulation of system 569 0.278182469 1 0.031028127 1 1 process GO:0001501 skeletal system 506 1 0.823129385 0.031162918 1 0.996446813 development GO:1903818 positive regulation of 15 1 1 0.031196003 1 1 voltage-gated potassium channel activity GO:0098742 cell-cell adhesion via 270 1 1 0.03127218 1 1 plasma-membrane adhesion molecules GO:0007269 neurotransmitter 167 1 1 0.032811717 1 1 secretion GO:0099643 signal release from 167 1 1 0.032811717 1 1 synapse GO:0050804 modulation of 418 0.844000933 1 0.034515558 0.102842968 1 chemical synaptic transmission GO:0099177 regulation of trans- 419 0.857332482 1 0.035278512 0.10434846 1 synaptic signaling GO:0035265 organ growth 195 1 1 0.037148224 1 1 GO:0044706 multi-multicellular 221 1 1 0.037148224 1 1 organism process GO:0021537 telencephalon 248 1 1 0.037418398 1 1 development GO:0016079 synaptic vesicle 123 1 1 0.038417362 1 1 exocytosis GO:0051960 regulation of nervous 883 0.107843848 1 0.039675644 0.335240873 1 system development GO:0072235 metanephric distal 7 1 1 0.039896554 1 1 tubule development GO:0120036 plasma membrane 1462 0.430289651 1 0.040423722 0.184216961 1 bounded cell projection organization GO:0060537 muscle tissue 395 1 1 0.041122974 1 1 development GO:0043062 extracellular structure 402 1 1 0.04968339 1 1 organization GO:0006928 movement of cell or 2138 8.70E−05 1 0.052850381 0.108871927 1 subcellular component GO:0030029 actin filament-based 732 0.028430549 1 0.055807618 1 1 process GO:0065008 regulation of 3891 1.72E−06 1 0.092517809 0.598967854 1 biological quality GO:0031589 cell-substrate adhesion 338 0.004206765 1 0.093681736 0.890858017 1 GO:0051239 regulation of 3093 2.64E−05 0.748743161 0.123095655 0.575098872 1 multicellular organismal process GO:2000026 regulation of 2064 0.030521352 0.966211545 0.211865167 0.24144412 1 multicellular organismal development GO:0007154 cell communication 6522 1.26E−09 1 0.2315925 0.035576453 1 GO:0048167 regulation of synaptic 173 0.756136312 1 0.247322371 0.025766984 1 plasticity GO:0009612 response to 204 0.016589491 1 0.264413515 1 1 mechanical stimulus GO:0048646 anatomical structure 1151 0.017059196 0.665596251 0.278694883 0.131591479 1 formation involved in morphogenesis GO:0007166 cell surface receptor 2974 2.22E−07 0.664638292 0.280083899 0.024 1 signaling pathway GO:0050793 regulation of 2607 0.00358275 0.489378401 0.299390486 0.136920059 1 developmental process GO:0045944 positive regulation of 1181 1 0.028430549 0.358787418 1 1 transcription by RNA polymerase II GO:0006937 regulation of muscle 164 0.004919038 1 0.405813243 1 1 contraction GO:0006810 transport 5065 6.95E−11 1 0.455598256 1 1 GO:0022603 regulation of 1098 0.027537974 0.80941255 0.48419276 0.376392302 1 anatomical structure morphogenesis GO:0023052 signaling 6475 5.74E−10 1 0.489378401 0.028424743 1 GO:0060284 regulation of cell 910 0.043655125 1 0.490789374 0.61494051 1 development GO:0051234 establishment of 5179 1.10E−10 1 0.491060511 1 1 localization GO:0051270 regulation of cellular 1052 0.001076518 1 0.604011244 1 1 component movement GO:0031644 regulation of 127 1 1 0.649678872 0.017681195 1 neurological system process GO:0051240 positive regulation of 1753 0.000807618 1 0.664849722 1 1 multicellular organismal process GO:0001568 blood vessel 756 0.027692049 1 0.665596251 0.190308867 1 development GO:0072358 cardiovascular system 799 0.039048021 1 0.670434263 0.08846971 1 development GO:0048518 positive regulation of 6054 2.12E−09 0.078665529 0.745168516 0.670434263 1 biological process GO:0010574 regulation of vascular 32 0.006085233 1 0.762819911 1 1 endothelial growth factor production GO:0050896 response to stimulus 9106 1.30E−09 0.767683656 0.762982012 0.125702334 1 GO:0001944 vasculature 790 0.032663645 1 0.778782489 0.263544992 1 development GO:0043410 positive regulation of 562 0.000386618 1 0.794945764 1 1 MAPK cascade GO:0010573 vascular endothelial 34 0.008756837 1 0.823129385 1 1 growth factor production GO:0045595 regulation of cell 1788 0.004325196 1 0.877494832 0.996446813 1 differentiation GO:1903523 negative regulation of 36 0.012075239 1 0.890858017 1 1 blood circulation GO:0045893 positive regulation of 1511 1 0.00087738 0.918797783 1 1 transcription, DNA- templated GO:1902680 positive regulation of 1597 1 0.00087738 0.922242032 1 1 RNA biosynthetic process GO:1903508 positive regulation of 1596 1 0.00086646 0.922242032 1 1 nucleic acid-templated transcription GO:0002223 stimulatory C-type 65 0.017009962 1 0.972458544 1 1 lectin receptor signaling pathway GO:0010628 positive regulation of 1957 1 0.004755649 0.995169577 1 1 gene expression GO:0040011 locomotion 1909 2.16E−05 1 0.995169577 0.474177846 1 GO:0002220 innate immune 68 0.022623601 1 0.996446813 1 1 response activating cell surface receptor signaling pathway GO:0010646 regulation of cell 3532 3.18E−07 0.996446813 0.996446813 0.007264557 1 communication GO:0048514 blood vessel 677 0.026184522 1 0.996446813 0.161086801 1 morphogenesis GO:0071495 cellular response to 1373 0.011622623 0.308597466 0.996446813 1 0.161929325 endogenous stimulus GO:0000122 negative regulation of 835 1 4.26E−10 1 1 1 transcription by RNA polymerase II GO:0000165 MAPK cascade 926 0.000542536 1 1 1 1 GO:0000186 activation of MAPKK 52 0.000574544 1 1 1 1 activity GO:0000271 polysaccharide 74 0.009838404 1 1 1 1 biosynthetic process GO:0000272 polysaccharide 23 0.007542869 1 1 1 1 catabolic process GO:0001525 angiogenesis 587 0.009359443 1 1 0.211865167 1 GO:0001702 gastrulation with 28 1 1 1 1 0.007070407 mouth forming second GO:0001774 microglial cell 33 0.007271618 1 1 1 1 activation GO:0001775 cell activation 1407 9.24E−23 0.890858017 1 1 1 GO:0001776 leukocyte homeostasis 88 0.03127218 1 1 1 1 GO:0001780 neutrophil homeostasis 16 0.012199993 1 1 1 1 GO:0001816 cytokine production 716 8.54E−07 0.243930235 1 1 1 GO:0001817 regulation of cytokine 647 9.86E−06 0.457630758 1 1 1 production GO:0001819 positive regulation of 422 0.000246192 1 1 1 1 cytokine production GO:0001932 regulation of protein 1427 3.03E−07 1 1 1 1 phosphorylation GO:0001934 positive regulation of 1008 1.75E−07 1 1 1 1 protein phosphorylation GO:0002218 activation of innate 252 3.46E−05 1 1 1 1 immune response GO:0002221 pattern recognition 179 0.004057705 1 1 1 1 receptor signaling pathway GO:0002224 toll-like receptor 131 0.01844494 1 1 1 1 signaling pathway GO:0002237 response to molecule 337 0.000205114 1 1 1 1 of bacterial origin GO:0002244 hematopoietic 111 1 0.002200796 1 1 1 progenitor cell differentiation GO:0002252 immune effector 1246 7.83E−19 1 1 1 1 process GO:0002253 activation of immune 645 4.02E−06 1 1 1 1 response GO:0002262 myeloid cell 146 0.041941486 0.025357726 1 1 1 homeostasis GO:0002263 cell activation 701 2.15E−17 1 1 1 1 involved in immune response GO:0002269 leukocyte activation 33 0.007271618 1 1 1 1 involved in inflammatory response GO:0002274 myeloid leukocyte 638 9.90E−23 1 1 1 1 activation GO:0002275 myeloid cell activation 540 3.02E−20 1 1 1 1 involved in immune response GO:0002283 neutrophil activation 488 6.49E−20 1 1 1 1 involved in immune response GO:0002366 leukocyte activation 697 1.62E−17 1 1 1 1 involved in immune response GO:0002367 cytokine production 95 0.016140011 1 1 1 1 involved in immune response GO:0002376 immune system 3074 1.22E−20 0.892839413 1 1 1 process GO:0002429 immune response- 414 0.006508093 1 1 1 1 activating cell surface receptor signaling pathway GO:0002443 leukocyte mediated 868 9.50E−17 1 1 1 1 immunity GO:0002444 myeloid leukocyte 548 5.49E−20 1 1 1 1 mediated immunity GO:0002446 neutrophil mediated 499 5.03E−20 1 1 1 1 immunity GO:0002520 immune system 912 0.009644361 0.000500171 1 1 0.405813243 development GO:0002521 leukocyte 501 0.212378102 0.017749668 1 1 1 differentiation GO:0002576 platelet degranulation 128 1.37E−05 1 1 1 1 GO:0002682 regulation of immune 1545 1.30E−09 1 1 1 1 system process GO:0002684 positive regulation of 1098 1.33E−08 1 1 1 1 immune system process GO:0002685 regulation of 180 0.013038389 1 1 1 1 leukocyte migration GO:0002687 positive regulation of 121 0.009448392 0.931021722 1 1 1 leukocyte migration GO:0002688 regulation of 109 0.013452901 1 1 1 1 leukocyte chemotaxis GO:0002697 regulation of immune 439 0.029881063 1 1 1 1 effector process GO:0002704 negative regulation of 45 0.037418398 1 1 1 1 leukocyte mediated immunity GO:0002718 regulation of cytokine 77 0.046629493 0.997059037 1 1 1 production involved in immune response GO:0002755 MyD88-dependent 36 0.001691861 1 1 1 1 toll-like receptor signaling pathway GO:0002757 immune response- 568 1.34E−05 1 1 1 1 activating signal transduction GO:0002758 innate immune 233 0.000110092 1 1 1 1 response-activating signal transduction GO:0002764 immune response- 599 8.40E−06 1 1 1 1 regulating signaling pathway GO:0002768 immune response- 445 0.003916178 1 1 1 1 regulating cell surface receptor signaling pathway GO:0002790 peptide secretion 582 0.028669624 1 1 1 1 GO:0005976 polysaccharide 109 0.003588731 1 1 1 1 metabolic process GO:0006022 aminoglycan 167 0.01778747 0.870337648 1 1 1 metabolic process GO:0006139 nucleobase-containing 6264 1 0.002380221 1 1 1 compound metabolic process GO:0006351 transcription, DNA- 3600 1 5.47E−06 1 1 1 templated GO:0006355 regulation of 3445 1 3.35E−06 1 1 1 transcription, DNA- templated GO:0006357 regulation of 2632 1 6.40E−06 1 1 1 transcription by RNA polymerase II GO:0006366 transcription by RNA 2768 1 8.50E−06 1 1 1 polymerase II GO:0006464 cellular protein 4066 1.66E−05 0.93115264 1 1 1 modification process GO:0006468 protein 1910 1.14E−06 1 1 0.635655637 1 phosphorylation GO:0006629 lipid metabolic 1415 0.034515558 1 1 1 1 process GO:0006725 cellular aromatic 6467 1 0.008831261 1 1 1 compound metabolic process GO:0006793 phosphorus metabolic 3236 1.32E−06 1 1 1 1 process GO:0006796 phosphate-containing 3209 7.74E−07 1 1 1 1 compound metabolic process GO:0006826 iron ion transport 61 0.044765835 1 1 1 1 GO:0006886 intracellular protein 1126 0.006155434 1 1 1 1 transport GO:0006887 exocytosis 897 1.08E−23 1 1 1 1 GO:0006897 endocytosis 783 2.44E−05 1 1 1 1 GO:0006909 phagocytosis 342 0.011958563 1 1 1 1 GO:0006914 autophagy 466 0.003701303 1 1 1 1 GO:0006915 apoptotic process 1966 0.001910279 1 1 1 1 GO:0006935 chemotaxis 619 0.01174754 1 1 1 1 GO:0006940 regulation of smooth 62 0.049426883 1 1 1 1 muscle contraction GO:0006950 response to stress 3908 5.50E−12 1 1 1 1 GO:0006952 defense response 1658 5.06E−10 1 1 1 1 GO:0006954 inflammatory response 780 4.60E−06 1 1 1 1 GO:0006955 immune response 2183 1.32E−19 1 1 1 1 GO:0007159 leukocyte cell-cell 327 0.002534667 1 1 1 1 adhesion GO:0007165 signal transduction 6031 1.51E−09 1 1 0.0521109 1 GO:0007169 transmembrane 694 0.006256544 1 1 0.996446813 1 receptor protein tyrosine kinase signaling pathway GO:0007249 I-kappaB kinase/NF- 258 0.00466681 1 1 1 1 kappaB signaling GO:0007264 small GTPase 547 0.00566515 1 1 1 1 mediated signal transduction GO:0007369 gastrulation 181 1 1 1 1 0.031028127 GO:0007568 aging 311 1 0.019378819 1 1 1 GO:0007596 blood coagulation 334 1.70E−08 1 1 1 1 GO:0007599 hemostasis 339 6.82E−09 0.901976979 1 1 1 GO:0008104 protein localization 2693 2.67E−05 1 1 1 1 GO:0008152 metabolic process 12421 1 0.031337146 1 1 1 GO:0008154 actin polymerization 206 0.043279439 1 1 1 1 or depolymerization GO:0008219 cell death 2232 0.003677466 1 1 1 1 GO:0009056 catabolic process 2490 1.66E−09 1 1 1 1 GO:0009057 macromolecule 1346 9.85E−07 1 1 1 1 catabolic process GO:0009058 biosynthetic process 6176 1 4.50E−06 1 1 1 GO:0009059 macromolecule 4998 1 1.65E−06 1 1 1 biosynthetic process GO:0009251 glucan catabolic 19 0.024975729 1 1 1 1 process GO:0009267 cellular response to 146 0.015656927 1 1 1 1 starvation GO:0009306 protein secretion 550 0.024183556 1 1 1 1 GO:0009605 response to external 2410 1.65E−09 1 1 1 1 stimulus GO:0009607 response to biotic 1014 3.97E−08 1 1 1 1 stimulus GO:0009611 response to wounding 655 9.77E−07 1 1 0.876970475 1 GO:0009615 response to virus 315 0.000527109 1 1 1 1 GO:0009617 response to bacterium 683 0.000497498 1 1 1 1 GO:0009636 response to toxic 513 0.03174739 1 1 1 1 substance GO:0009889 regulation of 4259 1 7.74E−06 1 1 1 biosynthetic process GO:0009890 negative regulation of 1625 1 1.64E−06 1 1 1 biosynthetic process GO:0009891 positive regulation of 1978 1 0.001496726 1 1 1 biosynthetic process GO:0009892 negative regulation of 3395 1 0.026947894 1 1 1 metabolic process GO:0009893 positive regulation of 3558 2.54E−05 0.065080058 1 0.796254883 1 metabolic process GO:0009894 regulation of catabolic 875 5.35E−06 0.995169577 1 1 1 process GO:0009896 positive regulation of 407 0.002076463 1 1 1 1 catabolic process GO:0009966 regulation of signal 3183 8.98E−08 0.668982235 1 0.022834087 1 transduction GO:0009967 positive regulation of 1606 4.08E−09 1 1 1 1 signal transduction GO:0009987 cellular process 16779 0.004881927 0.604011244 1 1 1 GO:0009991 response to 513 0.03174739 0.520071834 1 1 1 extracellular stimulus GO:0010033 response to organic 3172 1.22E−08 0.197199227 1 0.967833783 1 substance GO:0010243 response to 950 5.79E−05 1 1 1 1 organonitrogen compound GO:0010468 regulation of gene 4989 1 0.017606755 1 1 1 expression GO:0010543 regulation of platelet 30 0.027236556 1 1 1 1 activation GO:0010556 regulation of 4041 1 3.35E−06 1 1 1 macromolecule biosynthetic process GO:0010557 positive regulation of 1844 1 0.000674069 1 1 1 macromolecule biosynthetic process GO:0010558 negative regulation of 1536 1 3.22E−07 1 1 1 macromolecule biosynthetic process GO:0010562 positive regulation of 1124 3.91E−07 1 1 1 1 phosphorus metabolic process GO:0010604 positive regulation of 3299 1.05E−05 0.09101847 1 0.665596251 1 macromolecule metabolic process GO:0010605 negative regulation of 3164 1 0.009382245 1 1 1 macromolecule metabolic process GO:0010629 negative regulation of 2326 1 0.011891493 1 1 1 gene expression GO:0010638 positive regulation of 602 0.014166664 1 1 1 1 organelle organization GO:0010647 positive regulation of 1768 1.33E−08 1 1 0.957657142 1 cell communication GO:0010720 positive regulation of 529 0.026184522 1 1 1 1 cell development GO:0010821 regulation of 176 0.00334288 1 1 1 1 mitochondrion organization GO:0010822 positive regulation of 112 0.049884217 1 1 1 1 mitochondrion organization GO:0010941 regulation of cell death 1707 0.038843865 1 1 1 1 GO:0010942 positive regulation of 689 0.001270746 1 1 1 1 cell death GO:0010950 positive regulation of 171 0.022053268 1 1 0.933555354 1 endopeptidase activity GO:0010952 positive regulation of 189 0.007469011 1 1 1 1 peptidase activity GO:0012501 programmed cell death 2099 0.002691077 1 1 1 1 GO:0015031 protein transport 1974 1.57E−05 1 1 1 1 GO:0015669 gas transport 19 1 1 1 1 0.035229966 GO:0015833 peptide transport 2009 3.25E−05 1 1 1 1 GO:0016043 cellular component 6334 0.034533479 0.905458796 1 0.489378401 0.102751857 organization GO:0016045 detection of bacterium 12 0.037418398 1 1 1 1 GO:0016050 vesicle organization 314 0.003665448 1 1 1 1 GO:0016070 RNA metabolic 5106 1 0.001250472 1 1 1 process GO:0016192 vesicle-mediated 2058 7.47E−19 1 1 1 1 transport GO:0016310 phosphorylation 2303 9.46E−06 1 1 1 1 GO:0016477 cell migration 1537 1.08E−05 1 1 0.442735373 1 GO:0018130 heterocycle 4233 1 8.40E−06 1 1 1 biosynthetic process GO:0019219 regulation of 4013 1 5.63E−06 1 1 1 nucleobase-containing compound metabolic process GO:0019220 regulation of 1736 7.18E−07 1 1 1 1 phosphate metabolic process GO:0019221 cytokine-mediated 728 2.37E−07 1 1 1 1 signaling pathway GO:0019222 regulation of 7129 0.108871927 0.001496726 1 1 1 metabolic process GO:0019438 aromatic compound 4242 1 9.45E−06 1 1 1 biosynthetic process GO:0019538 protein metabolic 5855 0.000885922 1 1 0.93226801 1 process GO:0022604 regulation of cell 474 0.040355298 1 1 1 1 morphogenesis GO:0023014 signal transduction by 944 0.000451981 1 1 1 1 protein phosphorylation GO:0023051 regulation of signaling 3567 1.20E−07 0.918797783 1 0.00944828 1 GO:0023056 positive regulation of 1775 3.71E−09 1 1 0.984890815 1 signaling GO:0030097 hemopoiesis 819 0.034690044 0.000140896 1 1 0.686175641 GO:0030098 lymphocyte 344 1 0.026584093 1 1 1 differentiation GO:0030099 myeloid cell 405 0.04295607 0.134152259 1 1 1 differentiation GO:0030100 regulation of 260 0.013452901 1 1 1 1 endocytosis GO:0030155 regulation of cell 668 0.002919532 1 1 1 1 adhesion GO:0030163 protein catabolic 900 0.002021862 1 1 1 1 process GO:0030168 platelet activation 152 4.20E−07 0.996446813 1 1 1 GO:0030193 regulation of blood 77 0.002919532 1 1 1 1 coagulation GO:0030213 hyaluronan 13 0.049467321 0.93226801 1 1 1 biosynthetic process GO:0030218 erythrocyte 111 0.897478797 0.002200796 1 1 0.879865755 differentiation GO:0030220 platelet formation 20 1 0.023984508 1 1 1 GO:0030334 regulation of cell 910 0.001353029 1 1 1 1 migration GO:0030335 positive regulation of 519 4.00E−06 1 1 1 1 cell migration GO:0030593 neutrophil chemotaxis 101 0.007127455 1 1 1 1 GO:0030595 leukocyte chemotaxis 217 0.001379065 1 1 1 1 GO:0030851 granulocyte 32 1 0.027161313 1 1 1 differentiation GO:0031098 stress-activated protein 313 0.008881305 1 1 1 1 kinase signaling cascade GO:0031323 regulation of cellular 6127 0.000154745 5.63E−06 1 1 1 metabolic process GO:0031324 negative regulation of 2571 0.231941565 3.05E−05 1 1 1 cellular metabolic process GO:0031325 positive regulation of 3260 1.46E−05 0.026184522 1 1 1 cellular metabolic process GO:0031326 regulation of cellular 4184 1 6.54E−06 1 1 1 biosynthetic process GO:0031327 negative regulation of 1601 1 1.75E−06 1 1 1 cellular biosynthetic process GO:0031328 positive regulation of 1943 1 0.000816714 1 1 1 cellular biosynthetic process GO:0031329 regulation of cellular 765 6.52E−05 0.896075185 1 1 1 catabolic process GO:0031331 positive regulation of 347 0.006173714 0.989561623 1 1 1 cellular catabolic process GO:0031334 positive regulation of 259 0.029415629 0.973367399 1 1 1 protein complex assembly GO:0031347 regulation of defense 765 5.92E−06 1 1 1 1 response GO:0031349 positive regulation of 427 5.88E−06 1 1 1 1 defense response GO:0031399 regulation of protein 1821 2.37E−07 1 1 1 1 modification process GO:0031401 positive regulation of 1220 8.58E−07 1 1 1 1 protein modification process GO:0031646 positive regulation of 58 1 1 1 0.009678209 1 neurological system process GO:0031663 lipopolysaccharide- 56 0.006197688 1 1 1 1 mediated signaling pathway GO:0031667 response to nutrient 481 0.026184522 0.675996209 1 1 1 levels GO:0031668 cellular response to 258 0.062580021 0.032811717 1 1 1 extracellular stimulus GO:0031669 cellular response to 228 0.045842089 0.056922458 1 1 1 nutrient levels GO:0032092 positive regulation of 94 0.048234344 1 1 1 1 protein binding GO:0032101 regulation of response 840 0.001513988 1 1 1 1 to external stimulus GO:0032103 positive regulation of 297 0.024975729 1 1 1 1 response to external stimulus GO:0032147 activation of protein 323 3.00E−05 1 1 1 1 kinase activity GO:0032268 regulation of cellular 2616 1.27E−07 1 1 1 1 protein metabolic process GO:0032269 negative regulation of 1083 0.033725236 1 1 1 1 cellular protein metabolic process GO:0032270 positive regulation of 1584 8.98E−08 1 1 1 1 cellular protein metabolic process GO:0032496 response to 324 0.002200796 1 1 1 1 lipopolysaccharide GO:0032611 interleukin-1 beta 73 0.033780469 1 1 1 1 production GO:0032612 interleukin-1 87 0.029127228 1 1 1 1 production GO:0032637 interleukin-8 73 0.001845049 1 1 1 1 production GO:0032640 tumor necrosis factor 129 0.046405569 1 1 1 1 production GO:0032677 regulation of 66 0.000765005 1 1 1 1 interleukin-8 production GO:0032680 regulation of tumor 127 0.041122974 1 1 1 1 necrosis factor production GO:0032757 positive regulation of 46 0.000194198 1 1 1 1 interleukin-8 production GO:0032760 positive regulation of 73 0.033780469 1 1 1 1 tumor necrosis factor production GO:0032774 RNA biosynthetic 3659 1 5.18E−06 1 1 1 process GO:0032880 regulation of protein 963 9.45E−06 1 1 1 1 localization GO:0032940 secretion by cell 1478 1.08E−23 1 1 1 1 GO:0033036 macromolecule 3037 2.71E−05 1 1 1 1 localization GO:0033043 regulation of organelle 1237 0.018565448 0.869543798 1 1 1 organization GO:0033554 cellular response to 1928 0.000334829 1 1 1 1 stress GO:0033674 positive regulation of 552 1.79E−09 1 1 1 1 kinase activity GO:0034097 response to cytokine 1114 1.30E−07 1 1 1 1 GO:0034101 erythrocyte 120 1 0.004673466 1 1 0.940589364 homeostasis GO:0034109 homotypic cell-cell 76 0.04283723 0.996446813 1 1 1 adhesion GO:0034123 positive regulation of 22 0.043674424 1 1 1 1 toll-like receptor signaling pathway GO:0034134 toll-like receptor 2 16 0.000949328 1 1 1 1 signaling pathway GO:0034135 regulation of toll-like 11 0.027946094 1 1 1 1 receptor 2 signaling pathway GO:0034198 cellular response to 45 0.037418398 1 1 1 1 amino acid starvation GO:0034504 protein localization to 269 0.042659462 1 1 1 1 nucleus GO:0034613 cellular protein 1830 0.000731018 1 1 1 1 localization GO:0034641 cellular nitrogen 6998 1 0.006520896 1 1 1 compound metabolic process GO:0034645 cellular 4853 1 8.55E−06 1 1 1 macromolecule biosynthetic process GO:0034654 nucleobase-containing 4171 1 5.52E−06 1 1 1 compound biosynthetic process GO:0034976 response to 264 0.015996351 1 1 1 1 endoplasmic reticulum stress GO:0035556 intracellular signal 2817 1.30E−12 1 1 0.13056033 1 transduction GO:0036211 protein modification 4066 1.66E−05 0.93115264 1 1 1 process GO:0036230 granulocyte activation 505 4.83E−21 1 1 1 1 GO:0036344 platelet morphogenesis 21 1 0.028400502 1 1 1 GO:0038093 Fc receptor signaling 187 0.000173731 1 1 1 1 pathway GO:0038094 Fc-gamma receptor 138 0.02750321 1 1 1 1 signaling pathway GO:0040012 regulation of 1042 0.000435941 1 1 1 1 locomotion GO:0040017 positive regulation of 570 6.01E−06 1 1 1 1 locomotion GO:0042035 regulation of cytokine 94 0.048234344 0.24587016 1 1 1 biosynthetic process GO:0042060 wound healing 543 2.91E−08 1 1 1 1 GO:0042108 positive regulation of 57 0.031006288 1 1 1 1 cytokine biosynthetic process GO:0042110 T cell activation 451 0.000878164 1 1 1 1 GO:0042119 neutrophil activation 498 1.09E−20 1 1 1 1 GO:0042221 response to chemical 4641 6.82E−06 0.969666228 1 1 1 GO:0042325 regulation of 1536 7.74E−07 1 1 1 1 phosphorylation GO:0042327 positive regulation of 1053 7.48E−08 1 1 1 1 phosphorylation GO:0042330 taxis 621 0.012287565 1 1 1 1 GO:0042494 detection of bacterial 4 0.016140011 1 1 1 1 lipoprotein GO:0042592 homeostatic process 1867 0.022963874 1 1 0.996446813 0.345762208 GO:0042886 amide transport 2037 3.30E−05 1 1 1 1 GO:0042981 regulation of apoptotic 1572 0.029061136 1 1 1 1 process GO:0043065 positive regulation of 632 0.001982857 1 1 1 1 apoptotic process GO:0043067 regulation of 1586 0.024126389 1 1 1 1 programmed cell death GO:0043068 positive regulation of 636 0.001058108 1 1 1 1 programmed cell death GO:0043085 positive regulation of 1392 1.94E−09 1 1 1 1 catalytic activity GO:0043086 negative regulation of 795 0.036082289 1 1 1 1 catalytic activity GO:0043087 regulation of GTPase 481 0.049277258 1 1 1 1 activity GO:0043112 receptor metabolic 184 0.040035288 1 1 1 1 process GO:0043122 regulation of I-kappaB 226 0.018065402 1 1 1 1 kinase/NF-kappaB signaling GO:0043123 positive regulation of 181 0.00461387 1 1 1 1 I-kappaB kinase/NF- kappaB signaling GO:0043207 response to external 984 3.89E−07 1 1 1 1 biotic stimulus GO:0043249 erythrocyte maturation 15 1 0.006823622 1 1 1 GO:0043280 positive regulation of 126 0.038843865 1 1 1 1 cysteine-type endopeptidase activity involved in apoptotic process GO:0043281 regulation of cysteine- 209 0.007862201 1 1 1 1 type endopeptidase activity involved in apoptotic process GO:0043299 leukocyte 531 3.32E−21 1 1 1 1 degranulation GO:0043312 neutrophil 485 5.35E−20 1 1 1 1 degranulation GO:0043405 regulation of MAP 335 2.37E−06 1 1 1 1 kinase activity GO:0043406 positive regulation of 258 5.07E−06 1 1 1 1 MAP kinase activity GO:0043408 regulation of MAPK 776 1.92E−05 1 1 1 1 cascade GO:0043412 macromolecule 4269 8.87E−05 0.680217842 1 1 1 modification GO:0043434 response to peptide 417 0.015891141 1 1 1 1 hormone GO:0043549 regulation of kinase 837 5.71E−07 1 1 1 1 activity GO:0044093 positive regulation of 1736 5.74E−10 1 1 1 1 molecular function GO:0044237 cellular metabolic 11116 0.145299351 0.000447254 1 1 1 process GO:0044238 primary metabolic 11112 1 0.007170056 1 1 1 process GO:0044247 cellular polysaccharide 21 0.004611115 1 1 1 1 catabolic process GO:0044248 cellular catabolic 2204 5.16E−08 0.87520387 1 1 1 process GO:0044249 cellular biosynthetic 6015 1 5.07E−06 1 1 1 process GO:0044260 cellular 8207 0.110332446 0.000171375 1 1 1 macromolecule metabolic process GO:0044265 cellular 1118 0.015397049 0.748743161 1 1 1 macromolecule catabolic process GO:0044267 cellular protein 5151 0.000173216 0.901236414 1 1 1 metabolic process GO:0044271 cellular nitrogen 4905 1 1.09E−05 1 1 1 compound biosynthetic process GO:0044275 cellular carbohydrate 40 0.021226881 1 1 1 1 catabolic process GO:0045055 regulated exocytosis 788 1.08E−23 1 1 1 1 GO:0045087 innate immune 908 1.30E−09 1 1 1 1 response GO:0045088 regulation of innate 365 1.57E−07 1 1 1 1 immune response GO:0045089 positive regulation of 309 4.50E−06 1 1 1 1 innate immune response GO:0045123 cellular extravasation 54 0.000802516 1 1 1 1 GO:0045184 establishment of 2079 2.55E−05 1 1 1 1 protein localization GO:0045321 leukocyte activation 1257 4.94E−18 1 1 1 1 GO:0045597 positive regulation of 974 0.020370955 0.831969884 1 1 1 cell differentiation GO:0045785 positive regulation of 397 0.034129341 1 1 1 1 cell adhesion GO:0045859 regulation of protein 762 1.59E−07 1 1 1 1 kinase activity GO:0045860 positive regulation of 512 4.71E−09 1 1 1 1 protein kinase activity GO:0045862 positive regulation of 352 0.001187493 1 1 1 1 proteolysis GO:0045892 negative regulation of 1199 1 4.69E−09 1 0.469442217 1 transcription, DNA- templated GO:0045932 negative regulation of 27 0.017009962 1 1 1 1 muscle contraction GO:0045934 negative regulation of 1457 1 6.60E−07 1 0.923274969 1 nucleobase-containing compound metabolic process GO:0045935 positive regulation of 1862 1 0.001568173 1 1 1 nucleobase-containing compound metabolic process GO:0045937 positive regulation of 1124 3.91E−07 1 1 1 1 phosphate metabolic process GO:0045987 positive regulation of 32 0.036082289 1 1 1 1 smooth muscle contraction GO:0046483 heterocycle metabolic 6422 1 0.005792173 1 1 1 process GO:0046649 lymphocyte activation 713 0.019063382 0.345762208 1 1 1 GO:0046898 response to 4 1 0.013583116 1 1 1 cycloheximide GO:0046903 secretion 1614 1.08E−23 1 1 1 1 GO:0048010 vascular endothelial 91 0.038843865 1 1 1 1 growth factor receptor signaling pathway GO:0048013 ephrin receptor 80 0.000841417 1 1 1 1 signaling pathway GO:0048519 negative regulation of 5698 0.222729944 0.002085165 1 0.955645847 1 biological process GO:0048522 positive regulation of 5330 2.61E−08 0.01290706 1 0.892839413 1 cellular process GO:0048523 negative regulation of 4759 0.050048478 5.46E−05 1 0.681771571 1 cellular process GO:0048534 hematopoietic or 861 0.009678209 0.000236607 1 1 0.533565531 lymphoid organ development GO:0048583 regulation of response 4234 2.15E−08 1 1 0.400677758 1 to stimulus GO:0048584 positive regulation of 2373 3.55E−10 1 1 1 1 response to stimulus GO:0048821 erythrocyte 31 1 0.00036786 1 1 1 development GO:0048870 cell motility 1688 6.00E−05 1 1 0.629638536 1 GO:0048872 homeostasis of 248 0.019367226 0.052531007 1 1 1 number of cells GO:0050663 cytokine secretion 210 0.008352331 1 1 1 1 GO:0050701 interleukin-1 secretion 56 0.0280421 1 1 1 1 GO:0050702 interleukin-1 beta 48 0.011788736 1 1 1 1 secretion GO:0050776 regulation of immune 1022 2.37E−08 1 1 1 1 response GO:0050778 positive regulation of 823 1.39E−07 1 1 1 1 immune response GO:0050789 regulation of 11899 0.000110092 0.002209175 1 1 1 biological process GO:0050790 regulation of catalytic 2281 2.61E−08 1 1 0.899460453 1 activity GO:0050794 regulation of cellular 10828 4.85E−07 0.000104586 1 0.922242032 1 process GO:0050817 coagulation 340 7.31E−09 1 1 1 1 GO:0050818 regulation of 82 0.001058702 1 1 1 1 coagulation GO:0050820 positive regulation of 26 0.014166664 1 1 1 1 coagulation GO:0050863 regulation of T cell 305 0.015271277 1 1 1 1 activation GO:0050865 regulation of cell 587 0.017981836 1 1 1 1 activation GO:0050866 negative regulation of 184 0.040035288 1 1 1 1 cell activation GO:0050878 regulation of body 493 1.93E−05 1 1 1 0.966588903 fluid levels GO:0050900 leukocyte migration 478 0.000176302 1 1 1 1 GO:0051050 positive regulation of 936 0.016217447 1 1 1 1 transport GO:0051090 regulation of DNA- 412 0.026984947 0.792082077 1 1 1 binding transcription factor activity GO:0051091 positive regulation of 255 0.004012175 0.922242032 1 1 1 DNA-binding transcription factor activity GO:0051092 positive regulation of 146 1.92E−05 0.922242032 1 1 1 NF-kappaB transcription factor activity GO:0051094 positive regulation of 1395 0.038843865 0.830036129 1 1 1 developmental process GO:0051128 regulation of cellular 2457 3.72E−05 0.996446813 1 1 1 component organization GO:0051130 positive regulation of 1210 4.29E−05 1 1 1 1 cellular component organization GO:0051171 regulation of nitrogen 5907 0.008673409 5.89E−05 1 1 1 compound metabolic process GO:0051172 negative regulation of 2410 0.348615674 8.40E−06 1 1 1 nitrogen compound metabolic process GO:0051173 positive regulation of 3140 2.20E−05 0.072497165 1 1 1 nitrogen compound metabolic process GO:0051174 regulation of 1738 7.55E−07 1 1 1 1 phosphorus metabolic process GO:0051222 positive regulation of 402 0.001684062 1 1 1 1 protein transport GO:0051223 regulation of protein 672 0.023649461 1 1 1 1 transport GO:0051246 regulation of protein 2860 6.36E−08 1 1 1 1 metabolic process GO:0051247 positive regulation of 1681 1.05E−09 1 1 1 1 protein metabolic process GO:0051248 negative regulation of 1144 0.008981555 0.996446813 1 1 1 protein metabolic process GO:0051252 regulation of RNA 3738 1 2.45E−06 1 1 1 metabolic process GO:0051253 negative regulation of 1330 1 3.23E−08 1 0.633161182 1 RNA metabolic process GO:0051254 positive regulation of 1680 1 0.001413106 1 1 1 RNA metabolic process GO:0051272 positive regulation of 553 7.10E−06 1 1 1 1 cellular component movement GO:0051336 regulation of 1281 0.001796452 1 1 1 1 hydrolase activity GO:0051338 regulation of 941 2.18E−06 1 1 1 1 transferase activity GO:0051345 positive regulation of 763 0.002761855 1 1 1 1 hydrolase activity GO:0051347 positive regulation of 626 3.58E−08 1 1 1 1 transferase activity GO:0051607 defense response to 228 0.007642349 1 1 1 1 virus GO:0051641 cellular localization 2847 0.024959734 1 1 1 1 GO:0051674 localization of cell 1688 6.00E−05 1 1 0.629638536 1 GO:0051704 multi-organism 2485 3.72E−05 1 1 1 1 process GO:0051707 response to other 982 3.62E−07 1 1 1 1 organism GO:0051716 cellular response to 7432 3.67E−09 0.87520387 1 0.07488625 1 stimulus GO:0060079 excitatory postsynaptic 103 1 1 1 0.026564194 1 potential GO:0060218 hematopoietic stem 34 1 0.035278512 1 1 1 cell differentiation GO:0060255 regulation of 6630 0.443316572 0.00566515 1 1 1 macromolecule metabolic process GO:0060319 primitive erythrocyte 4 1 0.013583116 1 1 1 differentiation GO:0060326 cell chemotaxis 295 0.010056469 1 1 1 1 GO:0060341 regulation of cellular 879 0.024731895 1 1 1 1 localization GO:0060627 regulation of vesicle- 498 0.021966072 1 1 1 1 mediated transport GO:0060969 negative regulation of 35 1 0.040035288 1 1 1 gene silencing GO:0061003 positive regulation of 19 1 1 1 1 0.035229966 dendritic spine morphogenesis GO:0061024 membrane 846 0.012347546 1 1 1 1 organization GO:0061041 regulation of wound 134 0.022218406 1 1 1 1 healing GO:0061298 retina vasculature 18 1 1 1 1 0.031028127 development in camera-type eye GO:0061515 myeloid cell 67 0.52528845 7.08E−05 1 1 1 development GO:0061900 glial cell activation 40 0.003561051 1 1 1 1 GO:0061919 process utilizing 466 0.003701303 1 1 1 1 autophagic mechanism GO:0065007 biological regulation 12576 1.85E−06 0.018565448 1 0.356365961 1 GO:0065009 regulation of 3187 1.56E−06 1 1 0.478489879 1 molecular function GO:0070201 regulation of 715 0.011042006 1 1 1 1 establishment of protein localization GO:0070340 detection of bacterial 3 0.005055861 1 1 1 1 lipopeptide GO:0070498 interleukin-1-mediated 55 0.025766984 1 1 1 1 signaling pathway GO:0070527 platelet aggregation 57 0.031006288 1 1 1 1 GO:0070727 cellular 1840 0.00087738 1 1 1 1 macromolecule localization GO:0070887 cellular response to 3144 7.43E−11 0.481144832 1 1 0.916075135 chemical stimulus GO:0071216 cellular response to 229 2.35E−05 1 1 1 1 biotic stimulus GO:0071219 cellular response to 206 0.000693746 1 1 1 1 molecule of bacterial origin GO:0071222 cellular response to 199 0.012917217 1 1 1 1 lipopolysaccharide GO:0071260 cellular response to 78 1.92E−05 1 1 1 1 mechanical stimulus GO:0071310 cellular response to 2595 9.32E−10 0.179921038 1 1 0.883468397 organic substance GO:0071345 cellular response to 1028 1.59E−07 1 1 1 1 cytokine stimulus GO:0071346 cellular response to 178 0.030521352 1 1 1 1 interferon-gamma GO:0071375 cellular response to 307 0.016372759 1 1 1 1 peptide hormone stimulus GO:0071417 cellular response to 555 7.77E−06 1 1 1 0.519887215 organonitrogen compound GO:0071496 cellular response to 328 1.37E−05 0.133254818 1 1 1 external stimulus GO:0071621 granulocyte 120 0.002310269 1 1 1 1 chemotaxis GO:0071622 regulation of 42 0.026791027 1 1 1 1 granulocyte chemotaxis GO:0071675 regulation of 42 0.026791027 1 1 1 1 mononuclear cell migration GO:0071702 organic substance 2745 0.000324796 1 1 1 0.739725387 transport GO:0071705 nitrogen compound 2335 0.001910279 1 1 1 1 transport GO:0071706 tumor necrosis factor 135 0.007547433 1 1 1 1 superfamily cytokine production GO:0071840 cellular component 6506 0.075463572 0.686175641 1 0.698373195 0.046322431 organization or biogenesis GO:0071900 regulation of protein 496 1.59E−07 1 1 1 1 serine/threonine kinase activity GO:0071902 positive regulation of 323 2.62E−08 1 1 1 1 protein serine/threonine kinase activity GO:0072672 neutrophil 10 0.001140246 1 1 1 1 extravasation GO:0080090 regulation of primary 6069 0.004520227 9.52E−06 1 1 1 metabolic process GO:0080134 regulation of response 1452 6.85E−08 1 1 1 1 to stress GO:0080135 regulation of cellular 684 0.009359443 1 1 1 1 response to stress GO:0090087 regulation of peptide 701 0.0256708 1 1 1 1 transport GO:0090304 nucleic acid metabolic 5634 1 0.001513988 1 1 1 process GO:0090316 positive regulation of 158 0.010740006 1 1 1 1 intracellular protein transport GO:0097529 myeloid leukocyte 199 0.000433484 1 1 1 1 migration GO:0097530 granulocyte migration 134 0.000500171 1 1 1 1 GO:0097659 nucleic acid-templated 3642 1 3.98E−06 1 1 1 transcription GO:0098542 defense response to 548 0.041421832 1 1 1 1 other organism GO:0098543 detection of other 13 0.049467321 1 1 1 1 organism GO:0098657 import into cell 900 1.17E−05 1 1 0.996446813 1 GO:0098771 inorganic ion 722 0.039539873 1 1 0.875764979 1 homeostasis GO:0098976 excitatory chemical 8 1 1 1 0.013930431 1 synaptic transmission GO:0099565 chemical synaptic 111 1 1 1 0.037418398 1 transmission, postsynaptic GO:0150076 neuroinflammatory 47 0.0002357 1 1 1 1 response GO:1900046 regulation of 77 0.002919532 1 1 1 1 hemostasis GO:1901224 positive regulation of 70 0.026584093 1 1 1 1 NIK/NF-kappaB signaling GO:1901360 organic cyclic 6676 1 0.011793821 1 1 1 compound metabolic process GO:1901362 organic cyclic 4387 1 1.89E−05 1 1 1 compound biosynthetic process GO:1901564 organonitrogen 6899 9.53E−05 1 1 1 1 compound metabolic process GO:1901565 organonitrogen 1253 0.000953023 1 1 1 1 compound catabolic process GO:1901575 organic substance 2071 3.56E−07 1 1 1 1 catabolic process GO:1901576 organic substance 6099 1 2.53E−06 1 1 1 biosynthetic process GO:1901652 response to peptide 481 0.000512427 1 1 1 1 GO:1901653 cellular response to 356 0.000545066 1 1 1 1 peptide GO:1901698 response to nitrogen 1037 2.06E−05 1 1 1 1 compound GO:1901699 cellular response to 612 1.40E−05 1 1 1 0.402781503 nitrogen compound GO:1901700 response to oxygen- 1577 1.54E−05 1 1 1 1 containing compound GO:1901701 cellular response to 1092 5.13E−05 1 1 1 0.795980333 oxygen-containing compound GO:1902275 regulation of 175 1 0.038417362 1 1 1 chromatin organization GO:1902531 regulation of 1881 1.13E−09 1 1 1 1 intracellular signal transduction GO:1902533 positive regulation of 1077 3.91E−07 1 1 1 1 intracellular signal transduction GO:1902622 regulation of 31 0.03127218 1 1 1 1 neutrophil migration GO:1902679 negative regulation of 1251 1 1.26E−08 1 0.604011244 1 RNA biosynthetic process GO:1903037 regulation of 293 0.021687327 1 1 1 1 leukocyte cell-cell adhesion GO:1903506 regulation of nucleic 3499 1 2.97E−06 1 1 1 acid-templated transcription GO:1903507 negative regulation of 1249 1 1.21E−08 1 0.598967854 1 nucleic acid-templated transcription GO:1903510 mucopolysaccharide 110 0.014483105 1 1 1 1 metabolic process GO:1903555 regulation of tumor 131 0.01844494 1 1 1 1 necrosis factor superfamily cytokine production GO:1903557 positive regulation of 76 0.04283723 1 1 1 1 tumor necrosis factor superfamily cytokine production GO:1903747 regulation of 70 0.026584093 1 1 1 1 establishment of protein localization to mitochondrion GO:1903749 positive regulation of 56 0.0280421 1 1 1 1 establishment of protein localization to mitochondrion GO:1903827 regulation of cellular 508 0.000254902 1 1 1 1 protein localization GO:1903829 positive regulation of 318 0.004402893 1 1 1 1 cellular protein localization GO:1904951 positive regulation of 437 0.000496601 1 1 1 1 establishment of protein localization GO:1905268 negative regulation of 60 1 0.028370428 1 1 1 chromatin organization GO:1990266 neutrophil migration 112 0.001132309 1 1 1 1 GO:1990928 response to amino acid 47 0.046835063 1 1 1 1 starvation GO:2000112 regulation of cellular 3918 1 1.43E−05 1 1 1 macromolecule biosynthetic process GO:2000113 negative regulation of 1459 1 3.40E−07 1 1 1 cellular macromolecule biosynthetic process GO:2000116 regulation of cysteine- 232 0.00334288 1 1 1 1 type endopeptidase activity GO:2000145 regulation of cell 968 0.00318429 1 1 0.995169577 1 motility GO:2000147 positive regulation of 539 9.45E−06 1 1 1 1 cell motility GO:2000377 regulation of reactive 185 0.041941486 1 1 1 1 oxygen species metabolic process GO:2000463 positive regulation of 27 1 1 1 0.032162807 1 excitatory postsynaptic potential GO:2001056 positive regulation of 143 0.035857337 1 1 0.716801532 1 cysteine-type endopeptidase activity GO:2001141 regulation of RNA 3507 1 3.35E−06 1 1 1 biosynthetic process GO:2001233 regulation of apoptotic 391 0.014166664 1 1 1 1 signaling pathway

Time Series Analysis of Synovial Cell Marker Genes in RA Flares

To better characterize the relevance of the clusters identified by the time series analysis to synovitis (FIG. 3C), we examined them for enrichment in synovial cell subtypes characterized by scRNAseq. This analysis of 5265 single RA and osteoarthritis patient synovial cells identified four fibroblast, four B cell, six T cell, and four monocyte subpopulations (FIG. 4A). We identified approximately 200 marker genes that best distinguished each of 18 synovial cell types. AC2 was enriched with naive B cell genes (FIG. 4A and FIG. 17 ), and AC3 was enriched with three sublining fibroblast genes (CD34+, HLA-DR+, and DKK3+) (FIG. 4A). Two of these fibroblast subsets, CD34+ and HLA-DR+, are more abundant in inflamed synovium (20). We plotted expression of those transcripts that were common to both synovial sublining fibroblasts and AC3 over time and again noted their increased expression in blood one week prior to flare and decreased expression during flare (FIG. 4B, FIG. 18 , and Table 5).

Overall, 622 of 625 AC3 genes decreased during flare in patient 1, and a subset (194 genes) also decreased in flares from at least 3 out of 4 RA patients (and 22 genes in 4 out of 4 patients; FIG. 4C and Table 6), and permutation test indicated this overlap was greater than expected by chance (p=0.0001). Pathway analysis of the subset of 194 overlapping genes was again enriched for extracellular matrix and secreted glycoprotein.

We further tested whether cells that expressed surface markers of synovial fibroblasts were detectable in RA blood by flow cytometry (FIGS. 19 and 20 ). CD45−/CD31−/PDPN+ cells were increased in 19 additional RA patient blood relative to healthy controls (FIG. 4D). RNAseq of these cells confirmed they were enriched with AC3 cluster genes (FIG. 4E), synovial fibroblast genes (FIG. 21 ), and expressed classic synovial fibroblast genes such as FAP, DKK3, CDH11, as well as collagens and laminins (FIG. 22 ). Given their expression of classical mesenchymal surface markers and genes, we refer to these as PRe-Inflammatory Mesenchymal Cells (PRIME cells). Taken together, our observations suggest a model in which sequential activation of B cells activate PRIME cells just prior to flares, which are then evident at flare in inflamed synovium as inflammatory sublining fibroblasts (FIG. 5 ).

Discussion

We present longitudinal genomics as a strategy to study the antecedents to RA flare that may be generalizable to autoimmune diseases associated with waxing/waning clinical courses. We developed easy-to-use tools for patients to acquire both quantifiable clinical symptoms and molecular data at home over many years. This allowed us to capture data prior to the onset of clinical flares and retrospectively analyze it, identifying different RNA signatures (AC2 and AC3) evident in peripheral blood 1-2 weeks prior to flare.

The RNA signature of AC3 and sorted CD45−/CD31−/PDPN+circulating cells revealed enrichment for pathways including cartilage morphogenesis, endochondral bone growth, and extracellular matrix organization (FIG. 3E) and strongly overlapped with synovial sublining fibroblasts. We therefore propose antecedent PRIME cells are the precursors to inflammatory sublining fibroblasts previously found adjacent to blood vessels in inflamed RA synovium (21).

Significantly, inflamed sublining fibroblasts are pathogenic in an animal model of arthritis (22). Our discovery that human AC3 genes share molecular characteristics of sublining fibroblasts, together with the observation that these cells spike prior to flare but are less detectable in blood during flare (FIGS. 2 and 4 ) support a model in which PRIME cells immigrate acutely from blood to the synovium where they contribute to the inflammatory process (FIG. 5 ). This model is consistent with the observation that RA synovial fibroblasts can traffic to cartilage implants and are sufficient to passively transfer synovial inflammation in mice (23). Together our data suggest the mesenchymal signal detected in AC3 prior to flares represent a previously uncharacterized type of trafficking fibroblast that circulates in blood.

In addition, we observed a second RNA signature, AC2, activated in blood prior to the spike in AC3. AC2 bear RNA hallmarks of naive B cells. This finding is reminiscent of recent studies demonstrating autoreactive naive B cells are specifically activated in RA patients (24). While the triggers of these are unknown, infectious (for example bacterial or viral antigens), environmental or endogenous toxins (25-27) could provide a source of either specific antigens or activate pattern recognition receptors.

In conclusion, we demonstrate methods for densely collecting longitudinal clinical and gene expression data that can be used to discover changes in transcriptional profiles in the blood weeks prior to symptom onset. This approach led to discovery of PRIME cells, bearing hallmarks of synovial fibroblasts, which are more common in RA patients and increase in blood just prior to flares. In modeling all our data (FIG. 5 ), we suggest that prior to clinical flare, systemic B cell immune activation (detected as AC2) acts on PRIME cells, which traffic to the blood (detected as AC3) and subsequently to the synovial sublining during flares of disease activity. More generally, this work in RA provides an exemplar of an approach to waxing/waning inflammatory disease, suggesting a general strategy relevant to additional disorders such as lupus, multiple sclerosis, and vasculitis.

Tables 2, 5 and 6 referenced in the above are provided as follows:

TABLE 2 Pathway Analysis of Differentially Expressed Genes in Flare Versus Baseline sig sig ID TERM nGenes up.ngenes down.ngenes fdr.up fdr.down GO: 0002274 myeloid leukocyte activation 607 112 3 1.78E−29 1 GO: 0006955 immune response 1725 205 16 8.83E−29 1 GO: 0032940 secretion by cell 1354 176 12 8.83E−29 1 GO: 0043299 leukocyte degranulation 510 100 3 1.04E−28 1 GO: 0036230 granulocyte activation 486 97 3 1.74E−28 1 GO: 0001775 cell activation 1250 166 14 2.26E−28 1 GO: 0002275 myeloid cell activation involved in immune response 520 100 3 2.26E−28 1 GO: 0002376 immune system process 2531 260 31 2.26E−28 1 GO: 0002446 neutrophil mediated immunity 482 96 3 2.26E−28 1 GO: 0042119 neutrophil activation 480 96 3 2.26E−28 1 GO: 0046903 secretion 1468 183 13 2.41E−28 1 GO: 0043312 neutrophil degranulation 469 94 3 5.05E−28 1 GO: 0002444 myeloid leukocyte mediated immunity 527 100 3 5.52E−28 1 GO: 0002283 neutrophil activation involved in immune response 472 94 3 7.33E−28 1 GO: 0002366 leukocyte activation involved in immune response 652 111 5 4.28E−27 1 GO: 0002263 cell activation involved in immune response 655 111 5 6.10E−27 1 GO: 0045321 leukocyte activation 1111 150 10 2.96E−26 1 GO: 0006887 exocytosis 857 128 5 4.51E−26 1 GO: 0002443 leukocyte mediated immunity 726 116 5 5.52E−26 1 GO: 0002252 immune effector process 1063 145 7 8.77E−26 1 GO: 0045055 regulated exocytosis 755 118 4 1.23E−25 1 GO: 0016192 vesicle-mediated transport 1859 186 26 1.74E−17 1 GO: 0006950 response to stress 3333 273 39 5.46E−15 1 GO: 0050896 response to stimulus 7448 500 104 5.71E−15 1 GO: 0023052 signaling 5257 380 73 5.88E−14 1 GO: 0007165 signal transduction 4852 356 65 1.41E−13 1 GO: 0007154 cell communication 5297 379 74 3.76E−13 1 GO: 0009611 response to wounding 571 78 17 1.05E−12 0.129037518 GO: 0002684 positive regulation of immune system process 896 104 9 1.19E−12 1 GO: 0048584 positive regulation of response to stimulus 1994 181 22 1.19E−12 1 GO: 0051716 cellular response to stimulus 6105 420 85 1.63E−12 1 GO: 0002682 regulation of immune system process 1283 130 12 9.76E−12 1 GO: 0002253 activation of immune response 494 69 1 1.47E−11 1 GO: 0050776 regulation of immune response 831 96 8 1.89E−11 1 GO: 0050778 positive regulation of immune response 653 82 5 1.89E−11 1 GO: 0070887 cellular response to chemical stimulus 2747 224 40 2.59E−11 1 GO: 0045087 innate immune response 695 85 2 2.61E−11 1 GO: 0006952 defense response 1291 129 6 3.05E−11 1 GO: 0042060 wound healing 470 66 16 3.70E−11 0.059726283 GO: 0044093 positive regulation of molecular function 1569 147 20 6.93E−11 1 GO: 0080134 regulation of response to stress 1248 124 5 1.45E−10 1 GO: 0048583 regulation of response to stimulus 3614 272 43 2.27E−10 1 GO: 0050794 regulation of cellular process 9002 557 112 3.98E−10 1 GO: 0002757 immune response-activating signal transduction 426 60 1 4.31E−10 1 GO: 0048518 positive regulation of biological process 5233 362 71 4.36E−10 1 GO: 0006810 transport 4550 324 60 4.63E−10 1 GO: 0043085 positive regulation of catalytic activity 1257 123 17 4.63E−10 1 GO: 0065007 biological regulation 10244 616 138 4.63E−10 1 GO: 0051234 establishment of localization 4659 330 64 4.65E−10 1 GO: 0071310 cellular response to organic substance 2268 189 35 5.77E−10 1 GO: 0002764 immune response-regulating signaling pathway 455 62 2 6.66E−10 1 GO: 0035556 intracellular signal transduction 2501 202 29 1.41E−09 1 GO: 0009605 response to external stimulus 1977 169 23 1.55E−09 1 GO: 0048522 positive regulation of cellular process 4633 326 60 1.63E−09 1 GO: 0050790 regulation of catalytic activity 2027 171 24 3.27E−09 1 GO: 0010033 response to organic substance 2769 216 37 5.32E−09 1 GO: 0051179 localization 5807 386 89 1.23E−08 1 GO: 0050817 coagulation 299 45 7 2.98E−08 1 GO: 0042221 response to chemical 3714 268 52 3.46E−08 1 GO: 0007599 hemostasis 301 45 7 3.61E−08 1 GO: 0006954 inflammatory response 616 71 5 3.81E−08 1 GO: 0071900 regulation of protein serine/threonine kinase activity 453 58 3 3.85E−08 1 GO: 0043549 regulation of kinase activity 765 82 4 4.63E−08 1 GO: 0050789 regulation of biological process 9629 577 124 5.25E−08 1 GO: 1902531 regulation of intracellular signal transduction 1644 142 15 5.25E−08 1 GO: 0007596 blood coagulation 296 44 7 6.48E−08 1 GO: 1990266 neutrophil migration 80 21 3 1.44E−07 1 GO: 0002429 immune response-activating cell surface receptor signaling pathway 282 42 1 1.54E−07 1 GO: 0033674 positive regulation of kinase activity 508 61 2 1.54E−07 1 GO: 0031347 regulation of defense response 625 70 2 1.63E−07 1 GO: 0007166 cell surface receptor signaling pathway 2548 196 44 1.91E−07 0.908411304 GO: 0045859 regulation of protein kinase activity 696 75 4 2.14E−07 1 GO: 0097530 granulocyte migration 99 23 3 2.69E−07 1 GO: 0034097 response to cytokine 979 95 13 2.71E−07 1 GO: 0002768 immune response-regulating cell surface receptor signaling pathway 311 44 2 2.87E−07 1 GO: 0045088 regulation of innate immune response 335 46 0 3.13E−07 1 GO: 0071345 cellular response to cytokine stimulus 900 89 11 3.74E−07 1 GO: 0097529 myeloid leukocyte migration 156 29 4 4.42E−07 1 GO: 0065009 regulation of molecular function 2746 206 37 4.67E−07 1 GO: 0051338 regulation of transferase activity 863 86 5 4.88E−07 1 GO: 0043405 regulation of MAP kinase activity 306 43 2 5.15E−07 1 GO: 0071902 positive regulation of protein serine/threonine kinase activity 296 42 1 5.88E−07 1 GO: 0009607 response to biotic stimulus 775 79 4 8.36E−07 1 GO: 0032879 regulation of localization 2382 183 32 8.36E−07 1 GO: 0045860 positive regulation of protein kinase activity 469 56 2 8.36E−07 1 GO: 0009967 positive regulation of signal transduction 1414 122 17 1.12E−06 1 GO: 0051347 positive regulation of transferase activity 578 64 3 1.22E−06 1 GO: 0019221 cytokine-mediated signaling pathway 619 67 9 1.30E−06 1 GO: 0031349 positive regulation of defense response 379 48 1 1.72E−06 1 GO: 1902533 positive regulation of intracellular signal transduction 934 89 8 1.99E−06 1 GO: 0009966 regulation of signal transduction 2771 204 36 2.46E−06 1 GO: 0071621 granulocyte chemotaxis 86 20 2 2.75E−06 1 GO: 0030593 neutrophil chemotaxis 70 18 2 2.76E−06 1 GO: 0023056 positive regulation of signaling 1565 130 20 3.03E−06 1 GO: 1901700 response to oxygen-containing compound 1398 119 24 3.59E−06 1 GO: 0038093 Fc receptor signaling pathway 124 24 0 4.29E−06 1 GO: 0010942 positive regulation of cell death 615 65 5 5.18E−06 1 GO: 0023051 regulation of signaling 3129 223 39 5.75E−06 1 GO: 0010647 positive regulation of cell communication 1558 128 20 7.38E−06 1 GO: 0051707 response to other organism 747 74 4 7.77E−06 1 GO: 0043207 response to external biotic stimulus 748 74 4 8.13E−06 1 GO: 0008219 cell death 1947 152 18 8.16E−06 1 GO: 0043068 positive regulation of programmed cell death 569 61 5 8.16E−06 1 GO: 0002218 activation of innate immune response 233 34 0 8.37E−06 1 GO: 0051247 positive regulation of protein metabolic process 1469 122 16 8.56E−06 1 GO: 0010646 regulation of cell communication 3097 220 39 9.07E−06 1 GO: 0042110 T cell activation 414 49 4 9.07E−06 1 GO: 0040017 positive regulation of locomotion 481 54 8 1.08E−05 1 GO: 0043406 positive regulation of MAP kinase activity 237 34 1 1.23E−05 1 GO: 0009987 cellular process 13404 738 179 1.26E−05 1 GO: 0045089 positive regulation of innate immune response 284 38 0 1.31E−05 1 GO: 0043065 positive regulation of apoptotic process 565 60 5 1.38E−05 1 GO: 0040012 regulation of locomotion 848 80 13 1.54E−05 1 GO: 0012501 programmed cell death 1824 143 17 1.62E−05 1 GO: 0030335 positive regulation of cell migration 437 50 8 1.81E−05 1 GO: 0001816 cytokine production 653 66 4 1.87E−05 1 GO: 0006915 apoptotic process 1721 136 15 2.24E−05 1 GO: 0000186 activation of MAPKK activity 49 14 0 2.35E−05 1 GO: 1901698 response to nitrogen compound 931 85 12 2.35E−05 1 GO: 0033554 cellular response to stress 1775 139 14 2.63E−05 1 GO: 0032147 activation of protein kinase activity 294 38 1 3.02E−05 1 GO: 0050878 regulation of body fluid levels 433 49 8 3.25E−05 1 GO: 0051246 regulation of protein metabolic process 2429 178 24 3.25E−05 1 GO: 0002758 innate immune response-activating signal transduction 214 31 0 3.39E−05 1 GO: 0044248 cellular catabolic process 2063 156 13 3.41E−05 1 GO: 0051272 positive regulation of cellular component movement 462 51 8 3.82E−05 1 GO: 0051270 regulation of cellular component movement 855 79 14 3.97E−05 1 GO: 0030595 leukocyte chemotaxis 172 27 4 4.04E−05 1 GO: 2000147 positive regulation of cell motility 450 50 8 4.04E−05 1 GO: 0051092 positive regulation of NF-kappaB transcription factor activity 141 24 0 4.12E−05 1 GO: 0016477 cell migration 1236 104 27 4.44E−05 0.374640189 GO: 0042327 positive regulation of phosphorylation 892 81 7 5.46E−05 1 GO: 0050900 leukocyte migration 365 43 11 5.85E−05 0.391246998 GO: 0046649 lymphocyte activation 592 60 7 5.94E−05 1 GO: 0038094 Fc-gamma receptor signaling pathway 78 17 0 6.74E−05 1 GO: 0040011 locomotion 1566 124 33 7.17E−05 0.318994972 GO: 0032268 regulation of cellular protein metabolic process 2258 166 19 7.19E−05 1 GO: 0030168 platelet activation 146 24 3 7.58E−05 1 GO: 0009056 catabolic process 2322 169 21 0.000102197 1 GO: 0010562 positive regulation of phosphorus metabolic process 952 84 7 0.000102197 1 GO: 0045937 positive regulation of phosphate metabolic process 952 84 7 0.000102197 1 GO: 1901701 cellular response to oxygen-containing compound 984 86 22 0.000109264 0.469765814 GO: 0030334 regulation of cell migration 733 69 12 0.00011376 1 GO: 1901699 cellular response to nitrogen compound 563 57 12 0.000115015 1 GO: 0043408 regulation of MAPK cascade 648 63 6 0.000117993 1 GO: 0010243 response to organonitrogen compound 868 78 12 0.000126448 1 GO: 2000145 regulation of cell motility 780 72 13 0.000129242 1 GO: 0048870 cell motility 1366 110 28 0.000148918 0.546976326 GO: 0051674 localization of cell 1366 110 28 0.000148918 0.546976326 GO: 0071417 cellular response to organonitrogen compound 513 53 12 0.000148943 0.802988607 GO: 0051345 positive regulation of hydrolase activity 684 65 12 0.000166794 1 GO: 0098657 import into cell 757 70 16 0.000169245 0.853144703 GO: 0032880 regulation of protein localization 891 79 5 0.000173297 1 GO: 0032101 regulation of response to external stimulus 686 65 4 0.00018111 1 GO: 0001934 positive regulation of protein phosphorylation 849 76 7 0.00019432 1 GO: 0042325 regulation of phosphorylation 1329 107 11 0.000207752 1 GO: 0032270 positive regulation of cellular protein metabolic process 1378 110 11 0.000215866 1 GO: 1901652 response to peptide 426 46 7 0.000230098 1 GO: 0051049 regulation of transport 1607 124 21 0.000238452 1 GO: 0061024 membrane organization 736 68 8 0.000239587 1 GO: 0001932 regulation of protein phosphorylation 1225 100 11 0.000255758 1 GO: 0007159 leukocyte cell-cell adhesion 299 36 5 0.000269107 1 GO: 0009306 protein secretion 483 50 4 0.000269107 1 GO: 0002687 positive regulation of leukocyte migration 106 19 2 0.000274565 1 GO: 0006468 protein phosphorylation 1678 128 21 0.000274565 1 GO: 0031098 stress-activated protein kinase signaling cascade 287 35 0 0.000274565 1 GO: 0071216 cellular response to biotic stimulus 203 28 0 0.000274689 1 GO: 0065008 regulation of biological quality 3483 233 50 0.000278675 1 GO: 0033036 macromolecule localization 2816 195 28 0.000293603 1 GO: 0043410 positive regulation of MAPK cascade 473 49 4 0.000320863 1 GO: 0007155 cell adhesion 1250 101 32 0.000336573 0.040286053 GO: 0019220 regulation of phosphate metabolic process 1507 117 13 0.000343159 1 GO: 0031667 response to nutrient levels 421 45 3 0.000362009 1 GO: 0051174 regulation of phosphorus metabolic process 1509 117 13 0.000362009 1 GO: 0006909 phagocytosis 230 30 2 0.000365939 1 GO: 0002431 Fc receptor mediated stimulatory signaling pathway 80 16 0 0.000387008 1 GO: 0022610 biological adhesion 1257 101 32 0.000417147 0.043138 GO: 0050663 cytokine secretion 185 26 1 0.000425866 1 GO: 0023014 signal transduction by protein phosphorylation 797 71 10 0.000463812 1 GO: 0015031 protein transport 1831 136 17 0.000473998 1 GO: 0071496 cellular response to external stimulus 308 36 4 0.000486676 1 GO: 0060326 cell chemotaxis 234 30 5 0.0005037 1 GO: 0045184 establishment of protein localization 1934 142 19 0.000506381 1 GO: 0030155 regulation of cell adhesion 609 58 8 0.000509038 1 GO: 0045932 negative regulation of muscle contraction 20 8 0 0.000531728 1 GO: 0071702 organic substance transport 2515 176 27 0.000535431 1 GO: 0006914 autophagy 443 46 0 0.000565442 1 GO: 0061919 process utilizing autophagic mechanism 443 46 0 0.000565442 1 GO: 0051336 regulation of hydrolase activity 1127 92 16 0.000599955 1 GO: 0006897 endocytosis 645 60 15 0.000695764 0.678522254 GO: 0071260 cellular response to mechanical stimulus 75 15 2 0.000730688 1 GO: 0042886 amide transport 1885 138 19 0.000791641 1 GO: 0032612 interleukin-1 production 76 15 0 0.000859296 1 GO: 0006796 phosphate-containing compound metabolic process 2886 196 26 0.000875096 1 GO: 0032103 positive regulation of response to external stimulus 254 31 3 0.000898772 1 GO: 0002790 peptide secretion 508 50 6 0.000925557 1 GO: 0031401 positive regulation of protein modification process 1046 86 7 0.000925557 1 GO: 0010952 positive regulation of peptidase activity 171 24 1 0.000939318 1 GO: 0015833 peptide transport 1859 136 19 0.000941858 1 GO: 0009991 response to extracellular stimulus 453 46 3 0.000954405 1 GO: 1901653 cellular response to peptide 319 36 5 0.000970827 1 GO: 0034134 toll-like receptor 2 signaling pathway 16 7 0 0.001002353 1 GO: 1901564 organonitrogen compound metabolic process 6040 367 60 0.00113986 1 GO: 0009894 regulation of catabolic process 823 71 4 0.001233752 1 GO: 0000165 MAPK cascade 779 68 10 0.001302406 1 GO: 0002237 response to molecule of bacterial origin 299 34 2 0.001448175 1 GO: 0010950 positive regulation of endopeptidase activity 153 22 1 0.001467807 1 GO: 0016310 phosphorylation 2046 146 21 0.001473433 1 GO: 0006793 phosphorus metabolic process 2913 196 26 0.001490737 1 GO: 0009617 response to bacterium 490 48 3 0.001514023 1 GO: 0051046 regulation of secretion 679 61 5 0.001556577 1 GO: 0043067 regulation of programmed cell death 1367 105 13 0.001586821 1 GO: 2000116 regulation of cysteine-type endopeptidase activity 213 27 1 0.001630423 1 GO: 0030162 regulation of proteolysis 651 59 3 0.001650328 1 GO: 0051091 positive regulation of DNA-binding transcription factor activity 238 29 0 0.001674787 1 GO: 0042981 regulation of apoptotic process 1354 104 13 0.001724948 1 GO: 0002286 T cell activation involved in immune response 81 15 1 0.001731296 1 GO: 0070498 interleukin-1-mediated signaling pathway 54 12 0 0.001861726 1 GO: 0002685 regulation of leukocyte migration 156 22 2 0.001893805 1 GO: 0080135 regulation of cellular response to stress 625 57 3 0.001893805 1 GO: 0008150 biological_process 14638 780 198 0.001926983 1 GO: 0051704 multi-organism process 2076 147 14 0.001926983 1 GO: 0031399 regulation of protein modification process 1590 118 12 0.002015929 1 GO: 0010941 regulation of cell death 1477 111 13 0.00215311 1 GO: 1903037 regulation of leukocyte cell-cell adhesion 267 31 3 0.00215311 1 GO: 2001056 positive regulation of cysteine-type endopeptidase activity 135 20 1 0.002158532 1 GO: 0050867 positive regulation of cell activation 294 33 4 0.002322146 1 GO: 0008104 protein localization 2517 172 25 0.002381633 1 GO: 0050701 interleukin-1 secretion 47 11 0 0.002404685 1 GO: 0002688 regulation of leukocyte chemotaxis 94 16 2 0.002570483 1 GO: 0002223 stimulatory C-type lectin receptor signaling pathway 56 12 0 0.00259536 1 GO: 0032611 interleukin-1 beta production 65 13 0 0.00259536 1 GO: 0001817 regulation of cytokine production 589 54 4 0.002597853 1 GO: 0002694 regulation of leukocyte activation 446 44 4 0.002664683 1 GO: 0002696 positive regulation of leukocyte activation 284 32 4 0.002776889 1 GO: 0002433 immune response-regulating cell surface receptor 75 14 0 0.002791965 1 signaling pathway involved in phagocytosis GO: 0038096 Fc-gamma receptor signaling pathway involved in phagocytosis 75 14 0 0.002791965 1 GO: 0051770 positive regulation of nitric-oxide synthase biosynthetic process 13 6 0 0.002791965 1 GO: 0050863 regulation of T cell activation 285 32 3 0.002907125 1 GO: 0098542 defense response to other organism 365 38 0 0.002907125 1 GO: 0048519 negative regulation of biological process 4605 287 58 0.003060718 1 GO: 0010604 positive regulation of macromolecule metabolic process 2902 193 37 0.003155111 1 GO: 0045862 positive regulation of proteolysis 326 35 2 0.003155111 1 GO: 0051050 positive regulation of transport 851 71 13 0.003155111 1 GO: 0050851 antigen receptor-mediated signaling pathway 174 23 1 0.003171354 1 GO: 0031329 regulation of cellular catabolic process 715 62 0 0.003331165 1 GO: 0050865 regulation of cell activation 480 46 4 0.00340888 1 GO: 0052548 regulation of endopeptidase activity 341 36 2 0.003414219 1 GO: 0051223 regulation of protein transport 612 55 3 0.00355489 1 GO: 0001819 positive regulation of cytokine production 383 39 4 0.003612705 1 GO: 0051222 positive regulation of protein transport 370 38 2 0.003761834 1 GO: 0002220 innate immune response activating cell surface 59 12 0 0.004134873 1 receptor signaling pathway GO: 0038095 Fc-epsilon receptor signaling pathway 59 12 0 0.004134873 1 GO: 1903530 regulation of secretion by cell 631 56 4 0.004194911 1 GO: 0072672 neutrophil extravasation 9 5 1 0.004323416 1 GO: 0051240 positive regulation of multicellular organismal process 1506 111 22 0.004358097 1 GO: 0050702 interleukin-1 beta secretion 42 10 0 0.004383898 1 GO: 0002697 regulation of immune effector process 348 36 3 0.00505513 1 GO: 0002221 pattern recognition receptor signaling pathway 168 22 0 0.005171898 1 GO: 0009893 positive regulation of metabolic process 3126 204 38 0.005271532 1 GO: 0051239 regulation of multicellular organismal process 2648 177 41 0.005403955 1 GO: 0002755 MyD88-dependent toll-like receptor signaling pathway 35 9 0 0.005460604 1 GO: 1904951 positive regulation of establishment of protein localization 405 40 3 0.005460604 1 GO: 0002250 adaptive immune response 350 36 4 0.005571526 1 GO: 0016050 vesicle organization 296 32 1 0.005571526 1 GO: 0045785 positive regulation of cell adhesion 364 37 4 0.005594484 1 GO: 0052547 regulation of peptidase activity 364 37 2 0.005594484 1 GO: 0070201 regulation of establishment of protein localization 654 57 4 0.005626218 1 GO: 0006928 movement of cell or subcelIular component 1787 127 41 0.005781787 0.054108794 GO: 0002367 cytokine production involved in immune response 91 15 1 0.005828657 1 GO: 0071219 cellular response to molecule of bacterial origin 182 23 0 0.005892329 1 GO: 0061041 regulation of wound healing 113 17 0 0.006255149 1 GO: 0032757 positive regulation of interleukin-8 production 44 10 0 0.006351224 1 GO: 0071675 regulation of mononuclear cell migration 36 9 1 0.006679936 1 GO: 0051403 stress-activated MAPK cascade 260 29 0 0.006850318 1 GO: 0031323 regulation of cellular metabolic process 5315 322 54 0.006855097 1 GO: 0050707 regulation of cytokine secretion 160 21 1 0.006933616 1 GO: 0032496 response to lipopolysaccharide 287 31 2 0.007057627 1 GO: 0071705 nitrogen compound transport 2158 148 22 0.007275744 1 GO: 0010256 endomembrane system organization 384 38 3 0.00755502 1 GO: 0001776 leukocyte homeostasis 83 14 3 0.007636898 1 GO: 0002690 positive regulation of leukocyte chemotaxis 73 13 2 0.007690198 1 GO: 0071674 mononuclear cell migration 54 11 1 0.007715492 1 GO: 0098609 cell-cell adhesion 724 61 10 0.007721864 1 GO: 0000187 activation of MAPK activity 138 19 0 0.007734155 1 GO: 1903523 negative regulation of blood circulation 29 8 0 0.007734155 1 GO: 0050793 regulation of developmental process 2215 151 40 0.007916914 0.781661155 GO: 0071622 regulation of granulocyte chemotaxis 37 9 0 0.008028146 1 GO: 0090087 regulation of peptide transport 635 55 4 0.008354822 1 GO: 0051130 positive regulation of cellular component organization 1123 86 17 0.00860929 1 GO: 0031325 positive regulation of cellular metabolic process 2873 188 31 0.00899248 1 GO: 0001525 angiogenesis 445 42 6 0.0090508 1 GO: 0043087 regulation of GTPase activity 431 41 10 0.009152495 0.989075954 GO: 0071347 cellular response to interleukin-1 106 16 0 0.009152495 1 GO: 1903827 regulation of cellular protein localization 489 45 3 0.009195558 1 GO: 0016236 macroautophagy 266 29 0 0.00959439 1 GO: 1902622 regulation of neutrophil migration 30 8 0 0.009698552 1 GO: 0051249 regulation of lymphocyte activation 376 37 4 0.009906385 1 GO: 0050715 positive regulation of cytokine secretion 108 16 1 0.01128157 1 GO: 0009743 response to carbohydrate 204 24 3 0.011633007 1 GO: 0070302 regulation of stress-activated protein kinase signaling cascade 217 25 0 0.011808339 1 GO: 0048013 ephrin receptor signaling pathway 77 13 1 0.012690739 1 GO: 0007169 transmembrane receptor protein tyrosine kinase signaling pathway 616 53 11 0.012718363 1 GO: 0006464 cellular protein modification process 3634 229 39 0.012821559 1 GO: 0036211 protein modification process 3634 229 39 0.012821559 1 GO: 0043281 regulation of cysteine-type endopeptidase activity 193 23 0 0.12949805 1 involved in apoptotic process GO: 0051767 nitric-oxide synthase biosynthetic process 17 6 0 0.013035488 1 GO: 0051769 regulation of nitric-oxide synthase biosynthetic process 17 6 0 0.013035488 1 GO: 0070340 detection of bacterial lipopeptide 3 3 0 0.01315179 1 GO: 0002460 adaptive immune response based on somatic recombination 233 26 4 0.014276364 1 of immune receptors built from immunoglobin superfamily domains GO: 0002576 platelet degranulation 122 17 1 0.014503148 1 GO: 0050727 regulation of inflammatory response 314 32 2 0.014538693 1 GO: 0002224 toll-like receptor signaling pathway 123 17 0 0.01594757 1 GO: 0043123 positive regulation of I-kappaB kinase/NF-kappaB signaling 171 21 1 0.016024765 1 GO: 0045597 positive regulation of cell differentiation 858 68 15 0.017105336 1 GO: 0043547 positive regulation of GTPase activity 359 35 9 0.017159123 0.870477156 GO: 1903034 regulation of response to wounding 136 18 0 0.017874522 1 GO: 0051128 regulation of cellular component organization 2275 152 32 0.017920515 1 GO: 0030099 myeloid cell differentiation 360 35 5 0.017939107 1 GO: 0051173 positive regulation of nitrogen compound metabolic process 2771 180 34 0.01800847 1 GO: 0051094 positive regulation of developmental process 1201 89 21 0.018331106 1 GO: 0032677 regulation of interleukin-8 production 60 11 0 0.018411813 1 GO: 0070997 neuron death 305 31 1 0.018600627 1 GO: 0098543 detection of other organism 12 5 0 0.018875179 1 GO: 0051048 negative regulation of secretion 186 22 2 0.01891199 1 GO: 0009057 macromolecule catabolic process 1269 93 10 0.018999165 1 GO: 0045916 negative regulation of complement activation 7 4 0 0.01930961 1 GO: 0051056 regulation of small GTPase mediated signal transduction 306 31 6 0.01930961 1 GO: 0071476 cellular hypotonic response 7 4 0 0.01930961 1 GO: 2000258 negative regulation of protein activation cascade 7 4 0 0.01930961 1 GO: 0031663 lipopolysaccharide-mediated signaling pathway 51 10 0 0.019532324 1 GO: 0045123 cellular extravasation 51 10 3 0.019532324 0.669150896 GO: 0044267 cellular protein metabolic process 4551 277 47 0.019796909 1 GO: 1901575 organic substance catabolic process 1934 132 16 0.020007773 1 GO: 0006937 regulation of muscle contraction 138 18 1 0.020374992 1 GO: 0043434 response to peptide hormone 364 35 6 0.021070827 1 GO: 0050921 positive regulation of chemotaxis 115 16 2 0.02118087 1 GO: 0048523 negative regulation of cellular process 4113 253 52 0.021899591 1 GO: 0051051 negative regulation of transport 408 38 6 0.021899591 1 GO: 0010661 positive regulation of muscle cell apoptotic process 26 7 1 0.02192505 1 GO: 0019538 protein metabolic process 5067 304 56 0.022521548 1 GO: 0032872 regulation of stress-activated MAPK cascade 215 24 0 0.022830476 1 GO: 0035743 CD4-positive, alpha-beta T cell cytokine production 19 6 0 0.023474679 1 GO: 0033673 negative regulation of kinase activity 216 24 2 0.024339447 1 GO: 0009896 positive regulation of catabolic process 382 36 4 0.024678993 1 GO: 0080090 regulation of primary metabolic process 5208 311 55 0.025290196 1 GO: 0002718 regulation of cytokine production involved in immune response 73 12 1 0.025671832 1 GO: 0070482 response to oxygen levels 312 31 3 0.025671832 1 GO: 0042594 response to starvation 166 20 0 0.026248102 1 GO: 0043086 negative regulation of catalytic activity 669 55 6 0.026248102 1 GO: 0051348 negative regulation of transferase activity 244 26 2 0.026248102 1 GO: 0060759 regulation of response to cytokine stimulus 154 19 0 0.027030672 1 GO: 0050714 positive regulation of protein secretion 218 24 1 0.027033414 1 GO: 0090022 regulation of neutrophil chemotaxis 27 7 0 0.027033414 1 GO: 1904646 cellular response to amyloid-beta 27 7 1 0.027033414 1 GO: 0008283 cell proliferation 1761 121 28 0.027213333 1 GO: 0022407 regulation of cell-cell adhesion 356 34 4 0.027337401 1 GO: 0006508 proteolysis 1576 110 15 0.02922209 1 GO: 0072593 reactive oxygen species metabolic process 246 26 3 0.02922209 1 GO: 0043280 positive regulation of cysteine-type endopeptidase activity 119 16 0 0.029336158 1 involved in apoptotic process GO: 0002526 acute inflammatory response 131 17 0 0.029626108 1 GO: 0032868 response to insulin 233 25 4 0.029731739 1 GO: 0050708 regulation of protein secretion 387 36 2 0.030095053 1 GO: 0044247 cellular polysaccharide catabolic process 20 6 0 0.0301116 1 GO: 0090025 regulation of monocyte chemotaxis 20 6 1 0.0301116 1 GO: 0007160 cell-matrix adhesion 207 23 5 0.03037299 1 GO: 0006935 chemotaxis 537 46 11 0.031747962 1 GO: 0051251 positive regulation of lymphocyte activation 248 26 4 0.032193807 1 GO: 0035744 T-helper 1 cell cytokine production 8 4 0 0.032836459 1 GO: 0007264 small GTPase mediated signal transduction 523 45 10 0.032933819 1 GO: 0019222 regulation of metabolic process 5763 339 59 0.032947746 1 GO: 0042330 taxis 539 46 11 0.033892587 1 GO: 0050852 T cell receptor signaling pathway 133 17 1 0.034161479 1 GO: 0051090 regulation of DNA-binding transcription factor activity 377 35 2 0.036224025 1 GO: 0050920 regulation of chemotaxis 184 21 2 0.036574118 1 GO: 0009267 cellular response to starvation 134 17 0 0.0368303 1 GO: 0032637 interleukin-8 production 66 11 0 0.0368303 1 GO: 0061025 membrane fusion 134 17 0 0.0368303 1 GO: 1903901 negative regulation of viral life cycle 66 11 0 0.0368303 1 GO: 0090026 positive regulation of monocyte chemotaxis 14 5 1 0.037038122 1 GO: 0006469 negative regulation of protein kinase activity 198 22 2 0.03826875 1 GO: 0006979 response to oxidative stress 408 37 3 0.03826875 1 GO: 0036473 cell death in response to oxidative stress 77 12 0 0.03826875 1 GO: 0048534 hematopoietic or lymphoid organ development 777 61 11 0.03826875 1 GO: 0050818 regulation of coagulation 77 12 0 0.03826875 1 GO: 1903039 positive regulation of leukocyte cell-cell adhesion 198 22 3 0.03826875 1 GO: 0001782 B cell homeostasis 29 7 1 0.039601018 1 GO: 0001999 renal response to blood flow involved in circulatory 4 3 0 0.039601018 1 renin-angiotensin regulation of systemic arterial blood pressure GO: 0002001 renin secretion into blood stream 4 3 0 0.039601018 1 GO: 0042494 detection of bacterial lipoprotein 4 3 0 0.039601018 1 GO: 1903223 positive regulation of oxidative stress-induced neuron death 4 3 0 0.039601018 1 GO: 0002720 positive regulation of cytokine production involved 47 9 1 0.040286053 1 in immune response GO: 0070265 necrotic cell death 47 9 0 0.040286053 1 GO: 0030888 regulation of B cell proliferation 57 10 1 0.041271788 1 GO: 0032729 positive regulation of interferon-gamma production 57 10 1 0.041271788 1 GO: 0070527 platelet aggregation 57 10 0 0.041271788 1 GO: 0002822 regulation of adaptive immune response based on somatic 136 17 3 0.041344145 1 recombination of immune receptors built from immunoglobin superfamily domains GO: 0097300 programmed necrotic cell death 38 8 0 0.041379424 1 GO: 2000377 regulation of reactive oxygen species metabolic process 161 19 0 0.041379424 1 GO: 0006629 lipid metabolic process 1274 91 10 0.041845478 1 GO: 0043112 receptor metabolic process 174 20 5 0.041928718 1 GO: 0005976 polysaccharide metabolic process 101 14 1 0.043569205 1 GO: 0043122 regulation of I-kappaB kinase/NF-kappaB signaling 214 23 1 0.043569205 1 GO: 0022603 regulation of anatomical structure morphogenesis 912 69 18 0.043665082 1 GO: 0043412 macromolecule modification 3819 234 41 0.043813518 1 GO: 0071453 cellular response to oxygen levels 162 19 1 0.043846908 1 GO: 0000271 polysaccharide biosynthetic process 68 11 0 0.044145176 1 GO: 0050870 positive regulation of T cell activation 188 21 3 0.044145176 1 GO: 0071222 cellular response to lipopolysaccharide 175 20 0 0.044145176 1 GO: 1901214 regulation of neuron death 269 27 1 0.044145176 1 GO: 0070555 response to interleukin-1 125 16 1 0.044185913 1 GO: 0032269 negative regulation of cellular protein metabolic process 898 68 8 0.045826564 1 GO: 1904645 response to amyloid-beta 30 7 1 0.045966802 1 GO: 0000272 polysaccharide catabolic process 22 6 0 0.046155493 1 GO: 0090257 regulation of muscle system process 202 22 2 0.046184075 1 GO: 0006971 hypotonic response 9 4 0 0.049853168 1 GO: 0002673 regulation of acute inflammatory response 80 12 0 0.049885523 1 GO: 0051047 positive regulation of secretion 357 33 3 0.049885523 1 GO: 0016043 cellular component organization 5721 325 104 0.246813039 0.031675655 GO: 0006607 NLS-bearing protein import into nucleus 27 3 4 1 0.038603188 GO: 0030198 extracellular matrix organization 321 15 18 1 0.000116024 GO: 0030199 collagen fibril organization 47 2 7 1 0.000569572 GO: 0043062 extracellular structure organization 368 18 18 1 0.000615349 GO: 0060351 cartilage development involved in endochondral bone morphogenesis 41 1 5 1 0.02192505 GO: 0061138 morphogenesis of a branching epithelium 166 9 9 1 0.039793054 GO: 0061448 connective tissue development 233 6 13 1 0.002884637 GO: 0070208 protein heterotrimerization 12 0 3 1 0.040528723 GO: 0071229 cellular response to acid chemical 195 10 10 1 0.032559128 GO: 0071230 cellular response to amino acid stimulus 65 5 6 1 0.024461895

TABLE 5 Genes Common to Synovial Sublining Fibroblasts and AC3 cluster seneset ensembl symbol auc pct_nonzero pct_nonzero_other SC-F1 Fibroblast-CD34+ sublining (SC-F1) ENSG00000187955 COL14A1 0.88699058 0.98347107 0.30535427 SC-F1 Fibroblast-CD34+ sublining (SC-F1) ENSG00000164692 COL1A2 0.84468179 1 0.53280998 SC-F1 Fibroblast-CD34+ sublining (SC-F1) ENSG00000168542 COL3A1 0.82353841 1 0.53301127 SC-F1 Fibroblast-CD34+ sublining (SC-F1) ENSG00000130635 COL5A1 0.76918996 0.80991736 0.26348631 SC-F1 Fibroblast-CD34+ sublining (SC-F1) ENSG00000105664 COMP 0.72267741 0.5268595 0.09178744 SC-F1 Fibroblast-CD34+ sublining (SC-F1) ENSG00000133083 DCLK1 0.78673115 0.70041322 0.16807568 SC-F1 Fibroblast-CD34+ sublining (SC-F1) ENSG00000146648 EGFR 0.76375622 0.72933884 0.23007246 SC-F1 Fibroblast-CD34+ sublining (SC-F1) ENSG00000120738 EGR1 0.75381699 0.95041322 0.6507649 SC-F1 Fibroblast-CD34+ sublining (SC-F1) ENSG00000164694 FNDC1 0.7526103 0.63842975 0.15116747 SC-F1 Fibroblast-CD34+ sublining (SC-F1) ENSG00000131386 GALNT15 0.7329481 0.59297521 0.14351852 SC-F1 Fibroblast-CD34+ sublining (SC-F1) ENSG00000168079 SCARA5 0.74916074 0.78512397 0.28965378 SC-F1 Fibroblast-CD34+ sublining (SC-F1) ENSG00000137573 SULF1 0.73367922 0.67561983 0.23389694 SC-F1 Fibroblast-CD34+ sublining (SC-F1) ENSG00000091656 ZFHX4 0.77838039 0.71487603 0.2071256 SC-F2 Fibroblast-HLA-DRAhi sublining (SC-F2) ENSG00000187955 COL14A1 0.91760718 0.99165508 0.27044158 SC-F2 Fibroblast-HLA-DRAhi sublining (SC-F2) ENSG00000084636 COL16A1 0.87323477 0.83588317 0.10585252 SC-F2 Fibroblast-HLA-DRAhi sublining (SC-F2) ENSG00000164692 COL1A2 0.92139483 1 0.50961335 SC-F2 Fibroblast-HLA-DRAhi sublining (SC-F2) ENSG00000168542 COL3A1 0.93074592 1 0.50982464 SC-F2 Fibroblast-HLA-DRAhi sublining (SC-F2) ENSG00000134871 COL4A2 0.84125266 0.86648122 0.18761885 SC-F2 Fibroblast-HLA-DRAhi sublining (SC-F2) ENSG00000130635 COL5A1 0.88489277 0.95132128 0.21487429 SC-F2 Fibroblast-HLA-DRAhi sublining (SC-F2) ENSG00000133083 DCLK1 0.83131283 0.79972184 0.12655821 SC-F2 Fibroblast-HLA-DRAhi sublining (SC-F2) ENSG00000146648 EGFR 0.80327353 0.82058414 0.19142193 SC-F2 Fibroblast-HLA-DRAhi sublining (SC-F2) ENSG00000120738 EGR1 0.80507545 0.9930459 0.62941052 SC-F2 Fibroblast-HLA-DRAhi sublining (SC-F2) ENSG00000130508 PXDN 0.84330642 0.83171071 0.16670188 SC-F2 Fibroblast-HLA-DRAhi sublining (SC-F2) ENSG00000166444 ST5 0.83349089 0.81641168 0.15867315 SC-F3 Fibroblast-DKK3+ sublining (SC-F3) ENSG00000187955 COL14A1 0.85231287 0.96929825 0.33920368 SC-F3 Fibroblast-DKK3+ sublining (SC-F3) ENSG00000164692 COL1A2 0.90670253 1 0.55570444 SC-F3 Fibroblast-DKK3+ sublining (SC-F3) ENSG00000168542 COL3A1 0.90184724 1 0.55589587 SC-F3 Fibroblast-DKK3+ sublining (SC-F3) ENSG00000130635 COL5A1 0.91728082 0.98245614 0.28273354 SC-F3 Fibroblast-DKK3+ sublining (SC-F3) ENSG00000105664 COMP 0.81905082 0.71929825 0.10470904 SC-F3 Fibroblast-DKK3+ sublining (SC-F3) ENSG00000164694 FNDC1 0.8072182 0.76315789 0.16960184 SC-F3 Fibroblast-DKK3+ sublining (SC-F3) ENSG00000131386 GALNT15 0.81963055 0.76754386 0.15792496 SC-F3 Fibroblast-DKK3+ sublining (SC-F3) ENSG00000164294 GPX8 0.80951068 0.8245614 0.22396631 SC-F3 Fibroblast-DKK3+ sublining (SC-F3) ENSG00000167779 IGFBP6 0.83772643 0.78947368 0.16807044 SC-F3 Fibroblast-DKK3+ sublining (SC-F3) ENSG00000130508 PXDN 0.83692715 0.88157895 0.2270291 SC-F3 Fibroblast-DKK3+ sublining (SC-F3) ENSG00000168079 SCARA5 0.81990132 0.89035088 0.3093415 SC-F3 Fibroblast-DKK3+ sublining (SC-F3) ENSG00000137573 SULF1 0.83014503 0.86403509 0.24732006 SC-F3 Fibroblast-DKK3+ sublining (SC-F3) ENSG00000091656 ZFHX4 0.78976712 0.80263158 0.22817764

TABLE 6 Differential Gene Expression (Baseline versus Flare) of AC3 Genes Across Four RA Patients ensembl name name_source description p1.logFC p1.FDR ENSG00000002746 HECW1 HGNC Symbol “HECT, C2 and WW −0.324338654 0.572555903 domain containing E3 ubiquitin protein ligase 1 [Source: HGNC Symbol; Acc: HGNC: 22195]” ENSG00000004948 CALCR HGNC Symbol calcitonin receptor −0.383180659 0.456241297 [Source: HGNC Symbol; Acc: HGNC: 1440] ENSG00000006071 ABCC8 HGNC Symbol ATP binding cassette −0.439216452 0.462869018 subfamily C member 8 [Source: HGNC Symbol; Acc: HGNC: 59] ENSG00000006128 TAC1 HGNC Symbol tachykinin precursor −0.578738859 0.363924977 1 [Source: HGNC Symbol; Acc: HGNC: 11517] ENSG00000006210 CX3CL1 HGNC Symbol C-X3-C motif chemokine −0.471842178 0.456192862 ligand 1 [Source: HGNC Symbol; Acc: HGNC: 10647] ENSG00000006283 CACNA1G HGNC Symbol calcium voltage-gated −0.65282151 0.174308995 channel subunit alpha1 G [Source: HGNC Symbol; Acc: HGNC: 1394] ENSG00000006788 MYH13 HGNC Symbol myosin heavy chain −0.516406336 0.431394501 13 [Source: HGNC Symbol; Acc: HGNC: 7571] ENSG00000009709 PAX7 HGNC Symbol paired box7 [Source: HGNC −0.287566069 0.642117066 Symbol; Acc: HGNC: 8921] ENSG00000011677 GABRA3 HGNC Symbol gamma-aminobutyric acid −0.626857358 0.372582084 type A receptor alpha3 subunit [Source: HGNC Symbol; Acc: HGNC: 4077] ENSG00000015520 NPC1L1 HGNC Symbol NPC1 like intracellular cholesterol −0.449755668 0.428701424 transporter 1 [Source: HGNC Symbol; Acc: HGNC: 7898] ENSG00000018607 ZNF806 HGNC Symbol zinc finger protein −0.534986692 0.413023969 806 [Source: HGNC Symbol; Acc: HGNC: 33228] ENSG00000018625 ATP1A2 HGNC Symbol ATPase Na+/K+ −0.380151358 0.490411631 transporting subunit alpha 2 [Source: HGNC Symbol; Acc: HGNC: 800] ENSG00000019505 SYT13 HGNC Symbol synaptotagmin 13 [Source: HGNC −0.846079415 0.136236167 Symbol; Acc: HGNC: 14962] ENSG00000039139 DNAH5 HGNC Symbol dynein axonemal heavy chain 5 −0.56614922 0.362219403 [Source: HGNC Symbol; Acc: HGNC: 2950] ENSG00000039987 BEST2 HGNC Symbol bestrophin 2 [Source: HGNC −0.490981764 0.418968005 Symbol; Acc: HGNC: 17107] ENSG00000054356 PTPRN HGNC Symbol “protein tyrosine phosphatase, −0.476009808 0.236645395 receptor type N [Source: HGNC Symbol; Acc: HGNC: 9676]” ENSG00000060656 PTPRU HGNC Symbol “protein tyrosine phasphatase, −0.440933203 0.365704058 receptor type U [Source: HGNC Symbol; Acc: HGNC: 9683]” ENSG00000060709 RIMBP2 HGNC Symbol RIMS binding protein 2 [Source: HGNC −0.486388539 0.313754361 Symbol; Acc: HGNC: 30339] ENSG00000068078 FGFR3 HGNC Symbol fibroblast growth factor receptor 3 −0.474403299 0.318084941 [Source: HGNC Symbol; Acc: HGNC: 3690] ENSG00000069431 ABCC9 HGNC Symbol ATP binding cassette subfamily C member 9 −0.755222404 0.203283416 [Source: HGNC Symbol; Acc: HGNC: 60] ENSG00000070886 EPHA8 HGNC Symbol EPH receptor A8 [Source: HGNC −0.506558126 0.338093351 Symbol; Acc: HGNC: 3391] ENSG00000072041 SLC6A15 HGNC Symbol solute carrier family 6 member 15 −0.23655442 0.738227188 [Source: HGNC Symbol; Acc: HGNC: 13621] ENSG00000075891 PAX2 HGNC Symbol paired box 2 [Source: HGNC −0.768916818 0.140011294 Symbol; Acc: HGNC: 8616] ENSG00000077080 ACTL6B HGNC Symbol actin like 6B [Source: HGNC −0.59184773 0.349654025 Symbol; Acc: HGNC: 160] ENSG00000077522 ACTN2 HGNC Symbol actinin alpha 2 [Source: HGNC −0.423228174 0.460775497 Symbol; Acc: HGNC: 164] ENSG00000078295 ADCY2 HGNC Symbol adenylate cyclase 2 [Source: HGNC −0.360850534 0.538385903 Symbol; Acc: HGNC: 233] ENSG00000078549 ADCYAP1R1 HGNC Symbol ADCYAP receptor type I [Source: HGNC −0.265394484 0.711597682 Symbol; Acc: HGNC: 242] ENSG00000078898 BPIFB2 HGNC Symbol BPI fold containing family B member 2 −0.585629077 0.353356904 [Source: HGNC Symbol; Acc: HGNC: 16177] ENSG00000079112 CDH17 HGNC Symbol cadherin 17 [Source: HGNC −0.61532191 0.280203448 Symbol; Acc: HGNC: 1756] ENSG00000079841 RIMS1 HGNC Symbol regulating synaptic membrane exocytosis 1 −0.387854778 0.537171359 [Source: HGNC Symbol; Acc: HGNC: 17282] ENSG00000081248 CACNA1S HGNC Symbol calcium voltage-gated channel subunit alpha1 S −0.562402388 0.274520413 [Source: HGNC Symbol; Acc: HGNC: 1397] ENSG00000081800 SLC13A1 HGNC Symbol solute carrier family 13 member 1 −0.711148359 0.288065754 [Source: HGNC Symbol; Acc: HGNC: 10916] ENSG00000082175 PGR HGNC Symbol progesterone receptor −0.458317998 0.411160075 [Source: HGNC Symbol; Acc: HGNC: 8910] ENSG00000084636 COL16A1 HGNC Symbol collagen type XVI alpha 1 chain −0.798050487 0.059725925 [Source: HGNC Symbol; Acc: HGNC: 2193] ENSG00000088340 FER1L4 HGNC Symbol “fer-1 like family member 4, pseudogene −0.61617873 0.156310461 [Source: HGNC Symbol; Acc: HGNC: 15801]” ENSG00000089116 LHX5 HGNC Symbol LIM homeobox 5 [Source: HGNC −0.803770937 0.082896409 Symbol; Acc: HGNC: 14216] ENSG00000089199 CHGB HGNC Symbol chromogranin B [Source: HGNC −0.637146342 0.263673795 Symbol; Acc: HGNC: 1930] ENSG00000089225 TBX5 HGNC Symbol T-box 5 [Source: HGNC Symbol; Acc: −0.56322196 0.348010747 HGNC: 11604] ENSG00000091128 LAMB4 HGNC Symbol laminin subunit beta −0.488177715 0.356139517 4 [Source: HGNC Symbol; Acc: HGNC: 6491] ENSG00000091137 SLC2GA4 HGNC Symbol solute carrier family 26 member 4 −0.554256056 0.194213389 [Source: HGNC Symbol; Acc: HGNC: 8818] ENSG00000091656 ZFHX4 HGNC Symbol zinc finger homeobox −0.447229074 0.37818144 4 [Source: HGNC Symbol; Acc: HGNC: 30939] ENSG00000095587 TLL2 HGNC Symbol tolloid like 2 [Source: HGNC −0.409359463 0.40882038 Symbol; Acc: HGNC: 11844] ENSG00000095637 SORBS1 HGNC Symbol sorbin and SH3 domain containing 1 −0.324241573 0.084190364 [Source: HGNC Symbol; Acc: HGNC: 14565] ENSG00000099625 CBARP HGNC Symbol CACN beta subunit associated regulatory protein −0.611658751 0.305918323 [Source: HGNC Symbol; Acc: HGNC: 28617] ENSG00000100033 PRODH HGNC Symbol proline dehydrogenase −0.729963766 0.114187223 1 [Source: HGNC Symbol; Acc: HGNC: 9453] ENSG00000100065 CARD10 HGNC Symbol caspase recruitment domain family member 10 −0.704322375 0.116976682 [Source: HGNC Symbol; Acc: HGNC: 16422] ENSG00000100078 PLA2G3 HGNC Symbol phospholipase A2 group −0.153902704 0.855150771 III [Source: HGNC Symbol; Acc: HGNC: 17934] ENSG00000100312 ACR HGNC Symbol acrasin [Source: HGNC Symbol; −0.595590525 0.36766088 Acc: HGNC: 126] ENSG00000101004 NINL HGNC Symbol ninein like [Source: HGNC −0.461697247 0.040537083 Symbol; Acc: HGNC: 29163] ENSG00000101057 MYBL2 HGNC Symbol MYB proto-oncogene like −0.348283275 0.153757922 2 [Source: HGNC Symbol; Acc: HGNC: 7548] ENSG00000101203 COL2OA1 HGNC Symbol callagen type XX alpha 1 −0.611027042 0.16213506 chain [Source: HGNC Symbol; Acc: HGNC: 14670] ENSG00000101276 SLC52A3 HGNC Symbol solute carrier family 52 member 3 −0.619177881 0.319817117 [Source: HGNC Symbol; Acc: HGNC: 16187] ENSG00000101680 LAMA1 HGNC Symbol laminin subunit alpha −0.361627137 0.534718981 1 [Source: HGNC Symbol; Acc: HGNC: 6481] ENSG00000101871 MID1 HGNC Symbol midline 1 [Source: HGNC Symbol; −0.530388962 0.160205439 Acc: HGNC: 7095] ENSG00000102287 GABRE HGNC Symbol gamma-aminobutyric acid type A receptor −0.678792592 0.062885659 epsilon subunit [Source: HGNC Symbol; Acc: HGNC: 4085] ENSG00000102290 PCDH11X HGNC Symbol protocadherin 11 X-linked −0.646927871 0.279252696 [Source: HGNC Symbol; Acc: HGNC: 8656] ENSG00000102452 NALCN HGNC Symbol “sodiom leak channel, non-selective −0.587260069 0.349930169 [Source: HGNC Symbol; Acc: HGNC: 19082]” ENSG00000103647 CORO2B HGNC Symbol coronin 2B [Source: HGNC −0.364156888 0.361299257 Symbol; Acc: HGNC: 2256] ENSG00000103855 CD276 HGNC Symbol CD276 molecule [Source: HGNC −0.786492202 0.123693703 Symbol; Acc: HGNC: 19137] ENSG00000104055 TGM5 HGNC Symbol transglutaminase −0.744478896 0.156122955 5 [Source: HGNC Symbol; Acc: HGNC: 11781] ENSG00000104313 EYA1 HGNC Symbol EYA transcriptional coactivator −0.54795524 0.332328891 and phosphatase 1 [Source: HGNC Symbol; Acc: HGNC: 3519] ENSG00000104435 STMN2 HGNC Symbol stathmin 2 [Source: HGNC −0.538149899 0.377735541 Symbol; Acc: HGNC: 10577] ENSG00000104537 ANXA13 HGNC Symbol annexin A13 [Source: HGNC −0.298697524 0.666104371 Symbol; Acc: HGNC: 536] ENSG00000104967 NOVA2 HGNC Symbol NOVA alternative splicing regulator 2 −0.906429895 0.09600687 [Source: HGNC Symbol; Acc: HGNC: 7887] ENSG00000105290 APLP1 HGNC Symbol amyloid beta precursor like protein 1 −0.626897604 0.28126695 [Source: HGNC Symbol; Acc: HGNC: 597] ENSG00000105357 MYH14 HGNC Symbol myosin heavy chain −0.396112836 0.489919147 14 [Source: HGNC Symbol; Acc: HGNC: 23212] ENSG00000105392 CRX HGNC Symbol cone-rod homeobox −0.652077271 0.295697 [Source: HGNC Symbol; Acc: HGNC: 2383] ENSG00000105549 THEG HGNC Symbol theg spermatid protein −0.567300418 0.345650275 [Source: HGNC Symbol; Acc: HGNC: 13706] ENSG00000105605 CACNG7 HGNC Symbol calcium voltage-gated channel auxiliary subunit −0.825394915 0.173466676 gamma 7 [Source: HGNC Symbol; Acc: HGNC: 13626] ENSG00000105664 COMP HGNC Symbol cartilage oligomeric −0.799132187 0.027433298 matrix protein [Source: HGNC Symbol; Acc: HGNC: 2227] ENSG00000106078 COBL HGNC Symbol cordon-bleu WH2 rapeat −0.492882526 0.263675081 protein [Source: HGNC Symbol; Acc: HGNC: 22199] ENSG00000106304 SPAM1 HGNC Symbol sperm adhesion molecule −0.294698557 0.697359656 1 [Source: HGNC Symbol; Acc: HGNC: 11217] ENSG00000106648 GALNTL5 HGNC Symbol polypeptide N-acetylgalactosaminyltransferase −0.610689222 0.36620383 like 5 [Source: HGNC Symbol; Acc: HGNC: 21725] ENSG00000106689 LHX2 HGNC Symbol LIM homeobox 2 [Source: HGNC −0.630789543 0.278431947 Symbol; Acc: HGNC: 6594] ENSG00000107295 SH3GL2 HGNC Symbol “SH3 domain containing GRB2 like 2, endophilin −0.633805457 0.350665788 A1 [Source: HGNC Symbol; Acc: HGNC: 10831]” ENSG00000107807 TLX1 HGNC Symbol T cell leukemia homeobox −0.773774408 0.156228514 1 [Source: HGNC Symbol; Acc: HGNC: 5056] ENSG00000108018 SORCS1 HGNC Symbol sortilin relatad VPS10 domain containing −0.57187073 0.324225606 recaptor 1 [Source: HGNC Symbol; Acc: HGNC: 16697] ENSG00000109101 FDXN1 HGNC Symbol forkhead box N1 [Source: HGNC −0.551457548 0.309062169 Symbol; Acc: HGNC: 12765] ENSG00000110786 PTPN5 HGNC Symbol “protein tyrosine phosphatase, non-receptor type −0.733454811 0.20453153 5 [Source: HGNC Symbol; Acc: HGNC: 9657]” ENSG00000110887 DAO HGNC Symbol D-amino acid oxidase −0.519549208 0.394229719 [Source: HGNC Symbol; Acc: HGNC: 2671] ENSG00000110975 SYT10 HGNC Symbol synaptotagmin 10 −0.84217722 0.209970599 [Source: HGNC Symbol; Acc: HGNC: 19266] ENSG00000111262 KCNA1 HGNC Symbol potassium voltage-gated channel subfamily A −0.777520439 0.155026428 member 1 [Source: HGNC Symbol; Acc: HGNC: 6218] ENSG00000111799 COL12A1 HGNC Symbol collagen type XII alpha 1 −0.950476274 0.050268873 chain [Source: HGNC Symbol; Acc: HGNC: 2188] ENSG00000112186 CAP2 HGNC Symbol cyclase associated actin cytoskeleton −0.981736845 0.075743598 regulatory protein 2 [Source: HGNC Symbol; Acc: HGNC: 20039] ENSG00000112238 PRDM13 HGNC Symbol PR/SET domain 13 [Source: HGNC −0.71815787 0.166013748 Symbol; Acc: HGNC: 13998] ENSG00000112337 SLC17A2 HGNC Symbol solute carrier family 17 member 2 −0.701065633 0.275381582 [Source: HGNC Symbol; Acc: HGNC: 10930] ENSG00000112499 SLC22A2 HGNC Symbol solute carrier family 22 member 2 −0.585273619 0.283511169 [Source: HGNC Symbol; Acc: HGNC: 10966] ENSG00000114019 AMOTL2 HGNC Symbol angiomotin like 2 [Source: HGNC −0.638655464 0.208042203 Symbol; Acc: HGNC: 17812] ENSG00000115041 KCNIP3 HGNC Symbol potassium voltage-gated channel interacting −0.390671123 0.447854968 protein 3 [Source: HGNC Symbol; Acc: HGNC: 15523] ENSG00000115155 DTOF HGNC Symbol otoferlin [Source: HGNC Symbol; −0.549744866 0.121108939 Acc: HGNC: 8515] ENSG00000115648 MLPH HGNC Symbol melanophilin [Source: HGNC −0.344672976 0.607643704 Symbol; Acc: HGNC: 29643] ENSG00000116176 TPSG1 HGNC Symbol tryptase gamma 1 [Source: HGNC −0.696648839 0.249497404 Symbol; Acc: HGNC: 14134] ENSG00000116721 PRAMEF1 HGNC Symbol PRAME family member −0.909385699 0.148992939 1 [Source: HGNC Symbol; Acc: HGNC: 28840] ENSG00000116748 AMPD1 HGNC Symbol adenosine monophosphate deaminase 1 −0.630797468 0.331507314 [Source: HGNC Symbol; Acc: HGNC: 468] ENSG00000116833 NR5A2 HGNC Symbol nuclear receptor subfamily −0.796732603 0.066795635 5 group A member 2 [Source: HGNC Symbol; Acc: HGNC: 7984] ENSG00000117114 ADGRL2 HGNC Symbol adhesion G protein-coupled −0.80941013 0.08058928 receptor L2 [Source: HGNC Symbol; Acc: HGNC: 18582] ENSG00000117501 MRDH9 HGNC Symbol maestro heat like repeat −0.770913244 0.189731062 family member 9 [Source: HGNC Symbol; Acc: HGNC: 26287] ENSG00000118194 TNNT2 HGNC Symbol “troponin T2, cardiac −0.546314355 0.341682105 type [Source: HGNC Symbol; Acc: HGNC: 11949]” ENSG00000118733 DLFM3 HGNC Symbol olfactomedin 3 [Source: HGNC −0.801008321 0.203283416 Symbol; Acc: HGNC: 17990] ENSG00000119125 GDA HGNC Symbol guanine deaminase [Source: HGNC −0.747333668 0.215289278 Symbol; Acc: HGNC: 4212] ENSG00000119283 TRIM67 HGNC Symbol tripartite motif containing −0.692548587 0.118978734 67 [Source: HGNC Symbol; Acc: HGNC: 31859] ENSG00000119547 ONECUT2 HGNC Symbol one cut homeobox 2 [Source: HGNC −0.364064899 0.566813453 Symbol; Acc: HGNC: 8139] ENSG00000120251 GRIA2 HGNC Symbol glutamate ionotropic receptor −0.536759703 0.393639567 AMPA type subunit 2 [Scorce: HGNC Symbol; Acc: HGNC: 4572] ENSG00000120332 TNN HGNC Symbol tenascin N [Source: HGNC −0.797308943 0.154902439 Symbol; Acc: HGNC: 22942] ENSG00000120738 EGR1 HGNC Symbol Early growth response 0.387004274 0.467739752 1 [Source: HGNC Symbol; Acc: HGNC: 3238] ENSG00000121207 LRAT HGNC Symbol lecithin retino acyltransferase −0.478671249 0.448666849 [Source: HGNC Symbol; Acc: HGNC: 6685] ENSG00000122121 XPNPEP2 HGNC Symbol X-prolyl aminopeptidase −0.787898058 0.044947173 2 [Source: HGNC Symbol; Acc: HGNC: 12823] ENSG00000122778 KIAA1549 HGNC Symbol KIAA1549 [Source: HGNC Symbol; −0.516890518 0.188627673 Acc: HGNC: 22219] ENSG00000123243 ITIH5 HGNC Symbol inter-alpha-trypsin inhibitor −0.571168831 0.310806911 heavy chain family member 5 [Source: HGNC Symbol; Acc: HGNC: 21449] ENSG00000123572 NRK HGNC Symbol Nik related kinase −0.486349518 0.420910239 [Source: HGNC Symbol; Acc: HGNC: 25391] ENSG00000123977 DAW1 HGNC Symbol dyein assembly factor −0.654419876 0.276698737 with WD repeats 1 [Source: HGNC Sym8l; Acc: HGNC: 26383] ENSG00000124092 CTCFL HGNC Symbol CCCTC-binding factor −0.443308442 0.467030393 like [Source: HGNC Symbol; Acc: HGNC: 16234] ENSG00000124253 PCK1 HGNC Symbol phosphoenolpyruvate −0.720216315 0.251094538 carboxykinase 1 [Source: HGNC Symbol; Acc: HGNC: 8724] ENSG00000124440 HIF3A HGNC Symbol hypoxia inducible factor −0.743934584 0.170117086 3 alpha subunit [Source: HGNC Symbol; Acc: HGNC: 15825] ENSG00000124466 LYPD3 HGNC Symbol LY6/PLAUR domain containing 3 −0.753602142 0.045770113 [Source: HGNC Symbol; Acc: HGNC: 24880] ENSG00000124749 COL21A1 HGNC Symbol collagen type XXI alpha 1 chain −0.382109802 0.564364144 [Source: HGNC Symbol; Acc: HGNC: 17025] ENSG00000125255 SLC10A2 HGNC Symbol solute carrier family 10 member 2 −0.716865675 0.262922534 [Source: HGNC Symbol; Acc: HGNC: 10906] ENSG00000125492 BARHL1 HGNC Symbol BarH like homeobox −0.153912437 0.823410461 1 [Source: HGNC Symbol; Acc: HGNC: 953] ENSG00000125740 FOSB HGNC Symbol “FosB proto-oncogene, AP-1 0.168490461 0.82332641 transcription factor subunit [Source: HGNC Symbol; Acc: HGNC: 3797]” ENSG00000127129 EDN2 HGNC Symbol endothelin 2 [Source: HGNC −0.396163266 0.500431956 Symbol; Acc: HGNC: 3177] ENSG00000128573 FOXP2 HGNC Symbol forkhhead box P2 [Source: HGNC −0.425628065 0.496663487 Symbol; Acc: HGNC: 13875] ENSG00000128917 DLL4 HGNC Symbol delta like canonical Notch ligand 4 −0.702456843 0.136145207 [Source: HGNC Symbol; Acc: HGNC: 2910] ENSG00000129946 SHC2 HGNC Symbol SHC adaptor protein 2 [Source: HGNC −0.843357896 0.081141031 Symbol; Acc: HGNC: 29869] ENSG00000129990 SYT5 HGNC Symbol synaptotagmin 5 [Source: HGNC −0.81970687 0.165777377 Symbol; Acc: HGNC: 11513] ENSG00000130045 NXNL2 HGNC Symbol nucleoredoxin like 2 [Source: HGNC −0.59403632 0.278225713 Symbol; Acc: HGNC: 30482] ENSG00000130226 DPP6 HGNC Symbol dipeptidyl peptidase −0.086732477 0.915560052 like 6 [Source: HGNC Symbol; Acc: HGNC: 3010] ENSG00000130287 NCAN HGNC Symbol neurocan [Source: HGNC Symbol; −0.665537698 0.281766504 Acc: HGNC: 2465] ENSG00000130477 UNC13A HGNC Symbol unc-13 homolog A [Source: HGNC −0.493441944 0.309175629 Symbol; Acc: HGNC: 23150] ENSG00000130508 PXDN HGNC Symbol paroxidasin [Source: HGNC −0.703310686 0.123498419 Symbol; Acc: HGNC: 14966] ENSG00000130528 HRC HGNC Symbol histidine rich calcium −0.692484137 0.295903841 binding protein [Source: HGNC Symbol; Acc: HGNC: 5178] ENSG00000130540 SULT4A1 HGNC Symbol sulfotransferase −0.672278031 0.247255807 family 4A member 1 [Source: HGNC Symbol; Acc: HGNC: 14903] ENSG00000130635 COL5A1 HGNC Symbol collagan type V alpha 1 chain −1.059536259 0.005145777 [Source: HGNC Symbol; Acc: HGNC: 2209] ENSG00000131044 TTLL9 HGNC Symbol tubulin tyrosine ligase like 9 −0.648555965 0.080577407 [Source: HGNC Symbol; Acc: HGNC: 16118] ENSG00000131183 SLD34A1 HGNC Symbol solute carrier family 34 member 1 −0.553608399 0.222662052 [Source: HGNC Symbol; Acc: HGNC: 11019] ENSG00000131386 GALNT15 HGNC Symbol polypeptide −0.249199422 0.57936334 N-acetylgalactosaminyltransferase 15 [Source: HGNC Symbol; Acc: HGNC: 21531] ENSG00000132297 HHLA1 HGNC Symbol HERV-H LTR-associating −0.569303097 0.342618221 1 [Source: HGNC Symbol; Acc: HGNC: 4904] ENSG00000132321 IQCA1 HGNC Symbol IQ motif containing −0.491444835 0.302209736 with AAA domain 1 [Source: HGNC Symbol; Acc: HGNC: 26195] ENSG00000132639 SNAP25 HGNC Symbol synaptosome associated protein 25 −0.484337596 0.393579181 [Source: HGNC Symbol; Acc: HGNC: 11132] ENSG00000132972 RNF17 HGNC Symbol ring finger protein −0.539876442 0.323158258 17 [Source: HGNC Symbol; Acc: HGNC: 10060] ENSG00000132975 GPR12 HGNC Symbol G protein-coupled receptor −0.559671507 0.380221581 12 [Source: HGNC Symbol; Acc: HGNC: 4466] ENSG00000133083 DCLK1 HGNC Symbol doublecortin like kinase −0.693023499 0.188550204 1 [Source: HGNC Symbol; Acc: HGNC: 2700] ENSG00000133110 POSTN HGNC Symbol periostin [Source: HGNC Symbol; −1.95711401 0.00141871 Acc: HGNC: 16953] ENSG00000133124 IRS4 HGNC Symbol insulin recaptor substrate −0.486576337 0.415362956 4 [Source: HGNC Symbol; Acc: HGNC: 6128] ENSG00000133454 MYO18B HGNC Symbol myosin XVIIIB [Source: HGNC −0.556047442 0.119461856 Symbol; Acc: HGNC: 18150] ENSG00000134240 HMGCS2 HGNC Symbol 3-hydroxy-3-mathylglotaryl-CoA −0.569886518 0.322294501 synthase 2 [Source: HGNC Symbol; Acc: HGNC: 5008] ENSG00000134871 COL4A2 HGNC Symbol collagen type IV alpha 2 −0.723958351 0.078843824 chain [Source: HGNC Symbol; Acc: HGNC: 2203] ENSG00000135097 MSI1 HGNC Symbol musashi RNA binding protein −0.681488708 0.233945897 1 [Source: HGNC Symbol; Acc: HGNC: 7330] ENSG00000135409 AMHR2 HGNC Symbol anti-Mullerian hormone −0.365902217 0.57936334 receptor type 2 [Source: HGNC Symbol; Acc: HGNC: 465] ENSG00000135454 B4GALNT1 HGNC Symbol “beta-1,4-N-acetyl- −0.838916247 0.094761195 galactosaminyltransferase 1 [Source: HGNC Symbol; Acc: HGNC: 4117]” ENSG00000135472 FAIM2 HGNC Symbol Fas apoptotic inhibitory molecule 2 −0.683241772 0.166816589 [Source: HGNC Symbol; Acc: HGNC: 17067] ENSG00000135917 SLC19A3 HGNC Symbol solute carrier family 19 member 3 −0.940946251 0.097071433 [Source: HGNC Symbol; Acc: HGNC: 16266] ENSG00000135931 ARMC9 HGNC Symbol armadillo repeat containing −0.671965301 0.040773449 9 [Source: HGNC Symbol; Acc: HGNC: 20730] ENSG00000136352 NKX2-1 HGNC Symbol NK2 homeobox 1 [Source: HGNC −0.828072024 0.143100586 Symbol; Acc: HGNC: 11825] ENSG00000136535 TBR1 HGNC Symbol “T-box, brain −0.569543676 0.291480115 1 [Source: HGNC Symbol; Acc: HGNC: 11590]” ENSG00000136574 GATA4 HGNC Symbol GATA binding protein −0.431785431 0.458893715 4 [Source: HGNC Symbol; Acc: HGNC: 4173] ENSG00000136695 IL36RN HGNC Symbol interleukin 36 receptor antagonist −0.111115253 0.887785479 [Source: HGNC Symbol; Acc: HGNC: 15561] ENSG00000137203 TFAP2A HGNC Symbol transcription factor AP-2 alpha −0.719606178 0.197926578 [Source: HGNC Symbol; Acc: HGNC: 11742] ENSG00000137573 SULF1 HGNC Symbol sulfatase 1 [Source: HGNC −0.721098487 0.155312568 Symbol; Acc: HGNC: 20391] ENSG00000137648 TMPRSS4 HGNC Symbol transmembrane serine protease 4 −0.697399848 0.100309089 [Source: HGNC Symbol; Acc: HGNC: 11878] ENSG00000137766 UNC13C HGNC Symbol unc-13 homolog C [Source: HGNC −0.345910067 0.592753582 Symbol; Acc: HGNC: 23149] ENSG00000137819 PAQR5 HGNC Symbol progestin and adipoQ receptor −0.466098604 0.254871322 family member 5 [Source: HGNC Symbol; Acc: HGNC: 29645] ENSG00000138162 TACC2 HGNC Symbol transforming acidic −0.598212058 0.215791557 coiled-coil containing protein 2 [Source: HGNC Symbol; Acc: HGNC: 11523] ENSG00000138650 PCDH10 HGNC Symbol protocadherin 10 [Source: HGNC −0.339300016 0.604591273 Symbol; Acc: HGNC: 13404] ENSG00000138675 FGF5 HGNC Symbol fibroblast growth factor −0.605345738 0.362679738 5 [Source: HGNC Symbol; Acc: HGNC: 3683] ENSG00000138759 FRAS1 HGNC Symbol Fraser extracellular matrix −0.222946616 0.747027813 complex subunit 1 [Source: HGNC Symbol; Acc: HGNC: 19185] ENSG00000138892 TTLL8 HGNC Symbol tubulin tyrosine ligase like −0.897768588 0.092191936 8 [Source: HGNC Symbol; Acc: HGNC: 34000] ENSG00000139144 PIK3C2G HGNC Symbol phosphatidylinositol-4-phosphate −0.156595171 0.833030115 3-kinase catalytic subunit type 2 gamma [Source: HGNC Symbol; Acc: HGNC: 8973] ENSG00000139220 PPF1A2 HGNC Symbol PTPRF interacting protein alpha 2 −0.378470282 0.536515358 [Source: HGNC Symbol; Acc: HGNC: 9246] ENSG00000139767 SRRM4 HGNC Symbol serine/arginine repetitive matrix 4 −0.3343885 0.60876368 [Source: HGNC Symbol; Acc: HGNC: 29389] ENSG00000139865 TTC6 HGNC Symbol tetratricopeptide repeat domain 6 −0.541511875 0.377281018 [Source: HGNC Symbol; Acc: HGNC: 19739] ENSG00000140279 DUOX2 HGNC Symbol dual oxidase 2 [Source: HGNC −0.606118929 0.157597775 Symbol; Acc: HGNC: 13273] ENSG00000140527 WDR93 HGNC Symbol WD repeat domain 93 [Source: HGNC −0.510238996 0.36380238 Symbol; Acc: HGNC: 26924] ENSG00000140600 SH3GL3 HGNC Symbol “SH3 domain containing −0.348680711 0.57659031 GRB2 like 3, endophilin A3 [Source: HGNC Symbol; Acc: HGNC: 10832]” ENSG00000141434 MEP1B HGNC Symbol meprin A subunit beta [Source: HGNC −0.835496908 0.100858384 Symbol; Acc: HGNC: 7020] ENSG00000141668 CBLN2 HGNC Symbol cerebellin 2 precursor [Source: HGNC −0.408816792 0.515136432 Symbol; Acc: HGNC: 1544] ENSG00000141946 ZIM3 HGNC Symbol zinc finger imprinted 3 [Source: HGNC −0.553199901 0.418027916 Symbol; Acc: HGNC: 16366] ENSG00000142408 CACNG8 HGNC Symbol calcium voltage-gated channel auxiliary −0.654089337 0.014843697 subunit gamma 8 [Source: HGNC Symbol; Acc: HGNC: 13628] ENSG00000142449 FBN3 HGNC Symbol fibrillin 3 [Source: HGNC Symbol; −0.447192665 0.423778362 Acc: HGNC: 18794] ENSG00000142549 IGLON5 HGNC Symbol IgLON family member 5 [Source: HGNC −0.544479933 0.396566456 Symbol; Acc: HGNC: 34550] ENSG00000142611 PRDM16 HGNC Symbol PR/SET domain 16 [Source: HGNC −0.743776119 0.110743572 Symbol; Acc: HGNC: 14000] ENSG00000142623 PADI1 HGNC Symbol peptidyl arginine deiminase −0.616861527 0.338644986 1 [Source: HGNC Symbol; Acc: HGNC: 18367] ENSG00000142675 CNKSR1 HGNC Symbol connector enhancer of kinase −0.498623814 0.138703112 suppressor of Ras 1 [Source: HGNC Symbol; Acc: HGNC: 19700] ENSG00000142910 TINAGL1 HGNC Symbol tubulointerstitial nephritis −0.695391991 0.158084486 antigen like 1 [Source: HGNC Symbol; Acc: HGNC: 19168] ENSG00000143107 FNDC7 HGNC Symbol fibronectin type III −0.533451774 0.237237415 domain containing 7 [Source: HGNC Symbol; Acc: HGNC: 26668] ENSG00000143355 LHX9 HGNC Symbol LIM homeobox 9 [Source: HGNC −0.481769357 0.365710069 Symbol; Acc: HGNC: 14222] ENSG00000143450 OAZ3 HGNC Symbol ornithine decarboxylase antizyme 3 −0.731131098 0.04678294 [Source: HGNC Symbol; Acc: HGNC: 8097] ENSG00000143469 SYT14 HGNC Symbol synaptotagmin 14 [Source: HGNC −0.529977675 0.429615839 Symbol; Acc: HGNC: 23143] ENSG00000143867 DSR1 HGNC Symbol odd-skipped related −0.350861532 0.593032035 transciption factor 1 [Source: HGNC Symbol; Acc: HGNC: 8111] ENSG00000144115 THNSL2 HGNC Symbol threonine synthase like −0.327316109 0.532009313 2 [Source: HGNC Symbol; Acc: HGNC: 25602] ENSG00000144488 ESPNL HGNC Symbol espin like [Source: HGNC −0.577630971 0.253952213 Symbol; Acc: HGNC: 27937] ENSG00000144648 ACKR2 HGNC Symbol atypical chemokine receptor −0.477303908 0.045840057 2 [Source: HGNC Symbol; Acc: HGNC: 1565] ENSG00000144681 STAC HGNC Symbol SH3 and cysteine rich −0.560050605 0.182021883 domain [Source: HGNC Symbol; Acc: HGNC: 11353] ENSG00000144730 IL17RD HGNC Symbol interleukin 17 receptor −0.561060798 0.294689324 D [Source: HGNC Symbol; Acc: HGNC: 17616] ENSG00000144820 ADGRG7 HGNC Symbol adhesion G protein- −0.492313851 0.436137212 coupled receptor G7 [Source: HGNC Symbol; Acc: HGNC: 19241] ENSG00000144908 ALDH1L1 HGNC Symbol aldehyde dehydrogenase −0.412949182 0.450510268 1 family member L1 [Source: HGNC Symbol; Acc: HGNC: 3978] ENSG00000145242 EPHA5 HGNC Symbol EPH receptor A5 [Source: HGNC −0.56028279 0.397803597 Symbol; Acc: HGNC: 3389] ENSG00000145526 CDH18 HGNC Symbol cadherin 18 [Source: HGNC −0.747075064 0.255000128 Symbol; Acc: HGNC: 1757] ENSG00000145642 SHISAL2B HGNC Symbol shisa like 2B [Source: HGNC −1.490085497 0.001461516 Symbol; Acc: HGNC: 34236] ENSG00000145832 SLC25A48 HGNC Symbol solute carrier family 25 member 48 −0.382607037 0.565480846 [Source: HGNC Symbol; Acc: HGNC: 30451] ENSG00000146005 PSD2 HGNC Symbol pleckstrin and Sec7 −0.474391279 0.322965191 domain containing 2 [Source: HGNC Symbol; Acc: HGNC: 19092] ENSG00000146521 LINC01558 HGNC Symbol long intergenic non-protein −0.930731184 0.104996052 coding RNA 1558 [Source: HGNC Symbol; Acc: HGNC: 21235] ENSG00000146648 EGFR HGNC Symbol epidermal growth factor receptor −0.464347302 0.323083336 [Source: HGNC Symbol; Acc: HGNC: 3236] ENSG00000146839 ZAN HGNC Symbol zonadhesin (gene/pseudogene) −0.501901018 0.397563388 [Source: HGNC Symbol; Acc: HGNC: 12857] ENSG00000146950 SHROOM2 HGNC Symbol shroom family member −0.547481224 0.153040816 2 [Source: HGNC Symbol; Acc: HGNC: 630] ENSG00000147573 TRIM55 HGNC Symbol tripartite motif containing −0.406221036 0.529220394 55 [Source: HGNC Symbol; Acc: HGNC: 14215] ENSG00000147655 RSPD2 HGNC Symbol R-spondin 2 [Source: HGNC −0.425816624 0.490916964 Symbol; Acc: HGNC: 28583] ENSG00000147689 FAM83A HGNC Symbol family with sequence similarity −0.471846383 0.295535482 83 member A [Source: HGNC Symbol; Acc: HGNC: 28210] ENSG00000148357 HMCN2 HGNC Symbol hemicentin 2 [Source: HGNC −0.535566286 0.290997361 Symbol; Acc: HGNC: 21293] ENSG00000148408 CACNA1B HGNC Symbol calcium voltage-gated channel −0.501466836 0.284867302 subunit alpha1 B [Source: HGNC Symbol; Acc: HGNC: 1389] ENSG00000148513 ANKRD30A HGNC Symbol ankyrin repeat domain −0.871448013 0.164735964 30A [Source: HGNC Symbol; Acc: HGNC: 17234] ENSG00000148702 HABP2 HGNC Symbol hyaluronan binding protien −0.563571725 0.372582084 2 [Source: HGNC Symbol; Acc: HGNC: 4798] ENSG00000148342 SLC5A12 HGNC Symbol solute carrier family 5 member 12 −0.603891229 0.317483763 [Source: HGNC Symbol; Acc: HGNC: 28750] ENSG00000149633 KIAA1755 HGNC Symbol KIAA1755 [Source: HGNC −0.626269466 0.295535482 Symbol; Acc: HGNC: 29372] ENSG00000149654 CDH22 HGNC Symbol cadherin 22 [Source: HGNC −0.38181549 0.564754244 Symbol; Acc: HGNC: 13251] ENSG00000149926 FAM57B HGNC Symbol family with sequence similarity −0.826512075 0.147540268 57 member B [Source: HGNC Symbol; Acc: HGNC: 25295] ENSG00000150086 NA NA NA −0.381789129 0.543943649 ENSG00000150893 FREM2 HGNC Symbol FRAS1 related extracellular −0.27918432 0.685530175 matrix protein 2 [Source: HGNC Symbol; Acc: HGNC: 25396] ENSG00000151224 MAT1A HGNC Symbol methionine adenosyltransferase 1A −0.695829857 0.25715468 [Source: HGNC Symbol; Acc: HGNC: 6903] ENSG00000151474 FRMD4A HGNC Symbol FERM domain containing −0.266779579 0.183727706 4A [Source: HGNC Symbol; Acc: HGNC: 25491] ENSG00000151572 ANO4 HGNC Symbol anoctamin 4 [Source: HGNC −0.427488192 0.474520384 Symbol; Acc: HGNC: 23837] ENSG00000152822 GRM1 HGNC Symbol glutamate metabotropic receptor 1 −0.560201862 0.321661526 [Source: HGNC Symbol; Acc: HGNC: 4593] ENSG00000152910 CNTNAP4 HGNC Symbol contactin associated protein like 4 −0.144213925 0.859543676 [Source: HGNC Symbol; Acc: HGNC: 18747] ENSG00000153165 RGPD3 HGNC Symbol RANBP2-like and GRIP −0.866436535 0.003638752 domain containing 3 [Source: HGNC Symbol; Acc: HGNC: 32416] ENSG00000154099 DNAAF1 HGNC Symbol dynein axonemal assembly factor 1 −0.616204423 0.217696484 [Source: HGNC Symbol; Acc: HGNC: 30539] ENSG00000154478 GPR2G HGNC Symbol G protein-coupled receptor −0.494806205 0.406590218 26 [Source: HGNC Symbol; Acc: HGNC: 4481] ENSG00000155816 FMN2 HGNC Symbol formin 2 [Source: HGNC Symbol; −0.411373015 0.528626826 Acc: HGNC: 14074] ENSG00000156076 WIF1 HGNC Symbol WNT inhibitory factor 1 −0.701995845 0.249971053 [Source: HGNC Symbol; Acc: HGNC: 18081] ENSG00000156103 MMP16 HGNC Symbol matrix metallopeptidase −0.612940919 0.354953317 16 [Source: HGNC Symbol; Acc: HGNC: 7162] ENSG00000156222 SLC28A1 HGNC Symbol solute carrier family 28 member 1 −0.484780444 0.394304044 [Source: HGNC Symbol; Acc: HGNC: 11001] ENSG00000156413 FUT6 HGNC Symbol fucosyltransferase −0.59042874 0.291768914 6 [Source: HGNC Symbol; Acc: HGNC: 4017] ENSG00000156687 UNC5D HGNC Symbol unc-5 netrin receptor −0.678558516 0.219237459 D [Source: HGNC Symbol; Acc: HGNC: 18634] ENSG00000157214 STEAP2 HGNC Symbol STEAP2 metalloreductase −0.751247183 0.154094301 [Source: HGNC Symbol; Acc: HGNC: 17885] ENSG00000157423 HYDIN HGNC Symbol “HYDIN, axonemal central pair −0.339331962 0.501656362 apparatus protein [Source: HGNC Symbol; Acc: HGNC: 19368]” ENSG00000157927 RADIL HGNC Symbol Rap associating with DIL domain −0.542930642 0.218274573 [Source: HGNC Symbol; Acc: HGNC: 22226] ENSG00000158077 NLRP14 HGNC Symbol NLR family pyrin −0.399560124 0.501906622 domain containing 14 [Source: HGNC Symbol; Acc: HGNC: 22939] ENSG00000158125 XDH HGNC Symbol xanthine dehydrogenase −0.856880361 0.134914762 [Source: HGNC Symbol; Acc: HGNC: 12805] ENSG00000158258 CLSTN2 HGNC Symbol calsyntenin 2 [Source: HGNC −0.472246595 0.416827728 Symbol; Acc: HGNC: 17448] ENSG00000159251 ACTC1 HGNC Symbol “actin, alpha, −0.407779393 0.500035053 cardiac muscle 1 [Source: HGNC Symbol; Acc: HGNC: 143]” ENSG00000159337 PLA2G4D HGNC Symbol phospholipase A2 group −0.623844111 0.222267492 IVD [Source: HGNC Symbol; Acc: HGNC: 30038] ENSG00000159650 UROC1 HGNC Symbol urocanate hydratase −0.592610834 0.295239234 1 [Source: HGNC Symbol; Acc: HGNC: 26444] ENSG00000160460 SPTBN4 HGNC Symbol “spectrin beta, −0.681223524 0.093882704 non-erythrocytic 4 [Source: HGNC Symbol; Acc: HGNC: 14896]” ENSG00000160994 CCDC105 HGNC Symbol coiled-coil domain containing 105 −0.455466884 0.442646097 [Source: HGNC Symbol; Acc: HGNC: 26866] ENSG00000161103 AC008132.1 Clone-based −0.52329433 0.317152409 (Ensembl) gene ENSG00000161243 FBXO27 HGNC Symbol F-box protein 27 [Source: HGNC −0.817434469 0.165930422 Symbol; Acc: HGNC: 18753] ENSG00000161270 NPHS1 HGNC Symbol “NPHS1, nephrin [Source: HGNC −0.59448236 0.304121161 Symbol; Acc: HGNC: 7908]” ENSG00000161609 CCDC155 HGNC Symbol coiled-coil domain containing 155 −0.559684333 0.313465888 [Source: HGNC Symbol; Acc: HGNC: 26520] ENSG00000161682 FAM171A2 HGNC Symbol family with sequence −0.837068643 0.064801456 similarity 171 member A2 [Source: HGNC Symbol; Acc: HGNC: 30480] ENSG00000161940 BCL6B HGNC Symbol B cell CLL/lymphoma −0.733676229 0.061835527 6B [Source: HGNC Symbol; Acc: HGNC: 1002] ENSG00000162006 MSLNL HGNC Symbol mesothelin-like [Source: HGNC −0.824168169 0.109148457 Symbol; Acc: HGNC: 14170] ENSG00000162062 TEDC2 HGNC Symbol tubulin epsilon and delta complex 2 −0.659328987 0.150977424 [Source: HGNC Symbol; Acc: HGNC: 25849] ENSG00000162510 MATN1 HGNC Symbol “matrilin 1, cartilage −0.622999455 0.135310926 matrix protein [Source: HGNC Symbol; Acc: HGNC: 6907]” ENSG00000162631 NTNG1 HGNC Symbol netrin G1 [Source: HGNC Symbol; −0.620320047 0.187276211 Acc: HGNC: 23319] ENSG00000162706 CADM3 HGNC Symbol cell adhesion molecule −0.682331042 0.208106324 3 [Source: HGNC Symbol; Acc: HGNC: 17601] ENSG00000162738 VANGL2 HGNC Symbol VANGL planar cell polarity protein 2 −0.566370045 0.256539503 [Source: HGNC Symbol; Acc: HGNC: 15511] ENSG00000163395 IGFN1 HGNC Symbol immunoglobulin-like and −0.426568352 0.487780556 fibronectin type III domain containing 1 [Source: HGNC Symbol; Acc: HGNC: 24607] ENSG00000163689 C3orf67 HGNC Symbol chromosome 3 open reading frame 67 −0.465955576 0.282307208 [Source: HGNC Symbol; Acc: HGNC: 24763] ENSG00000163914 RHO HGNC Symbol rhodopsin [Source: HGNC −0.615499862 0.339797586 Symbol; Acc: HGNC: 10012] ENSG00000163975 MELTF HGNC Symbol melanotransferrin [Source: HGNC −0.416776144 0.260507627 Symbol; Acc: HGNC: 7037] ENSG00000163995 ABLIM2 HGNC Symbol actio binding LIM protein −0.520136403 0.063442539 family member 2 [Source: HGNC Symbol; Acc: HGNC: 19195] ENSG00000164093 PITX2 HGNC Symbol paired like homeodomain −0.857868402 0.057313592 2 [Source: HGNC Symbol; Acc: HGNC: 9005] ENSG00000164107 HAND2 HGNC Symbol heart and neural crest −0.753644576 0.223874451 derivatives expressed 2 [Source: HGNC Symbol; Acc: HGNC: 4808] ENSG00000164122 ASB5 HGNC Symbol ankyrin repeat and SOCS 0.079830425 0.915328605 box containing 5 [Source: HGNC Symbol; Acc: HGNC: 17180] ENSG00000164265 SCGB3A2 HGNC Symbol secretoglobin family 3A member 2 −0.511511464 0.009388442 [Source: HGNC Symbol; Acc: HGNC: 18391] ENSG00000164294 GPX8 HGNC Symbol glutathione peroxidase 8 (putative) −0.656518063 0.269654117 [Source: HGNC Symbol; Acc: HGNC: 33100] ENSG00000164393 ADGRF2 HGNC Symbol adhesion G protein-coupled −0.3870263 0.551210043 receptor F2 [Source: HGNC Symbol; Acc: HGNC: 18991] ENSG00000164692 COLIA2 HGNC Symbol collagen type I alpha 2 −1.329008825 0.002055954 chain [Source: HGNC Symbol; Acc: HGNC: 2198] ENSG00000164694 FNDC1 HGNC Symbol fibronectin type III −0.656127373 0.211972787 domain containing 1 [Source: HGNC Symbol; Acc: HGNC: 21184] ENSG00000164904 ALDH7A1 HGNC Symbol aldehyde dehydrogenase −0.490180368 0.202719915 7 family member A1 [Source: HGNC Symbol; Acc: HGNC: 877] ENSG00000165300 SLITRK5 HGNC Symbol SLIT and NTRK like family member 5 −0.675119097 0.028500813 [Source: HGNC Symbol; Acc: HGNC: 20295] ENSG00000165323 FAT3 HGNC Symbol FAT atypical cadherin −0.385540325 0.505923328 3 [Source: HGNC Symbol; Acc: HGNC: 23112] ENSG00000165379 LRFN5 HGNC Symbol leucine rich repeat and −0.642769127 0.318351819 fibronectin type III domain containing 5 [Source: HGNC Symbol; Acc: HGNC: 20360] ENSG00000165495 PKNOX2 HGNC Symbol PGX/knotted 1 homeobox −0.172065851 0.813551285 2 [Source: HGNC Symbol; Acc: HGNC: 16714] ENSG00000165566 AMER2 HGNC Symbol APC membrane recruitment protein 2 −0.383500908 0.550047859 [Source: HGNC Symbol; Acc: HGNC: 26360] ENSG00000165757 JCAD HGNC Symbol junctional cadherin 5 associated −0.687536793 0.05310314 [Source: HGNC Symbol; Acc: HGNC: 23283] ENSG00000165816 VWA2 HGNC Symbol von Willebrand factor −0.616958529 0.228018985 A domain containing 2 [Source: HGNC Symbol; Acc: HGNC: 24709] ENSG00000165966 PDZRN4 HGNC Symbol PDZ domain containing ring finger 4 −0.710133651 0.283637569 [Source: HGNC Symbol; Acc: HGNC: 30552] ENSG00000165970 SLC6A5 HGNC Symbol solute carrier family 6 member 5 −0.441556406 0.467030393 [Source: HGNC Symbol; Acc: HGNC: 11051] ENSG00000165973 NELL1 HGNC Symbol neural EGFL like 1 [Source: HGNC −0.775652603 0.220165101 Symbol; Acc: HGNC: 7750] ENSG00000166118 SPATA19 HGNC Symbol spermatogenesis associated −0.717800429 0.27315415 19 [Source: HGNC Symbol; Acc: HGNC: 30614] ENSG00000166159 LRTM2 HGNC Symbol leucine rich repeats −0.85369222 0.085585739 and transmembrane domains 2 [Source: HGNC Symbol; Acc: HGNC: 32443] ENSG00000166292 TMEM100 HGNC Symbol transmembrane protein −0.250984168 0.758168139 100 [Source: HGNC Symbol; Acc: HGNC: 25607] ENSG00000166391 MDGAT2 HGNC Symbol monoacylglycerol O-acyltransferase 2 −0.648731495 0.319053284 [Source: HGNC Symbol; Acc: HGNC: 23248] ENSG00000166444 ST5 HGNC Symbol suppression of tumorigenicity −0.623988928 0.08234925 5 [Source: HGNC Symbol; Acc: HGNC: 11350] ENSG00000166473 PKD1L2 HGNC Symbol polycystin 1 like 2 −0.290071825 0.668311557 (gene/pseudogene) [Source: HGNC Symbol; Acc: HGNC: 21715] ENSG00000166558 SLC38A8 HGNC Symbol solute carrier family −0.565390451 0.349528978 38 member 8 [Source: HGNC Symbol; Acc: HGNC: 32434] ENSG00000166596 CFAP52 HGNC Symbol cilia and flagella associated −0.373333127 0.567527075 protein 52 [Source: HGNC Symbol; Acc: HGNC: 16053] ENSG00000166689 PLEKHA7 HGNC Symbol pleckstrin homology domain −0.295527396 0.24002465 containing A7 [Source: HGNC Symbol; Acc: HGNC: 27049] ENSG00000166863 TAC3 HGNC Symbol tachykinin 3 [Source: HGNC −0.725563817 0.198940702 Symbol; Acc: HGNC: 11521] ENSG00000166869 CHP2 HGNC Symbol calcineurin like EF-hand protein 2 −0.947768021 0.112210394 [Source: HGNC Symbol; Acc: HGNC: 24927] ENSG00000166984 TCP10L2 HGNC Symbol t-complex 10 like 2 [Source: HGNC −0.754572409 0.150977424 Symbol; Acc: HGNC: 21254] ENSG00000167654 ATCAY HGNC Symbol “ATCAY, caytaxin [Source: HGNC −0.90959213 0.089473968 Symbol; Acc: HGNC: 779]” ENSG00000167723 TRPV3 HGNC Symbol transient receptor potential −0.563018449 0.047202728 cation channel subfamily V member 3 [Source: HGNC Symbol; Acc: HGNC: 18084] ENSG00000167757 KLK11 HGNC Symbol kallikrein related peptidase 11 −0.877178887 0.126229199 [Source: HGNC Symbol; Acc: HGNC: 6359] ENSG00000167779 IGFBP6 HGNC Symbol insulin like growth factor −0.44480682 0.307541999 binding protein 6 [Source: HGNC Symbol; Acc: HGNC: 5475] ENSG00000167798 C3P1 HGNC Symbol complement component 3 −0.397404693 0.575036428 precursor pseudogene [Source: HGNC Symbol; Acc: HGNC: 34414] ENSG00000168077 SCARA3 HGNC Symbol scavenger receptor class −0.633708326 0.238072641 A member 3 [Source: HGNC Symbol; Acc: HGNC: 19000] ENSG00000168079 SCARA5 HGNC Symbol scavenger receptor class −0.678863321 0.111887496 A member 5 [Source: HGNC Symbol; Acc: HGNC: 28701] ENSG00000168356 SCN11A HGNC Symbol sodium voltage-gated −0.418872904 0.366781722 channel alpha subunit 11 [Source: HGNC Symbol; Acc: HGNC: 10583] ENSG00000168367 LINC00917 HGNC Symbol long intergenic non-protein −0.11663907 0.89274309 coding RNA 917 [Source: HGNC Symbol; Acc: HGNC: 48607] ENSG00000168481 LGI3 HGNC Symbol leucine rich repeat LGI −0.573256523 0.302289133 family member 3 [Source: HGNC Symbol; Acc: HGNC: 18711] ENSG00000168484 SFTPC HGNC Symbol surfactant protein −1.037382046 0.063132935 C [Source: HGNC Symbol; Acc: HGNC: 10802] ENSG00000168542 COL3A1 HGNC Symbol collagen type III alpha 1 chain −1.474761932 0.012911146 [Source: HGNC Symbol; Acc: HGNC: 2201] ENSG00000168907 PLA2G4F HGNC Symbol phospholipase A2 group −0.587140187 0.299414708 IVF [Source: HGNC Symbol; Acc: HGNC: 27396] ENSG00000168959 GRM5 HGNC Symbol glutamate metabotropic receptor 5 −0.453630369 0.440906003 [Source: HGNC Symbol; Acc: HGNC: 4597] ENSG00000169126 ARMC4 HGNC Symbol armadillo repeat containing −0.575622675 0.299414708 4 [Source: HGNC Symbol; Acc: HGNC: 25583] ENSG00000169169 CPT1C HGNC Symbol carnitine palmitoyltransferase 1C −0.341160496 0.476106903 [Source: HGNC Symbol; Acc: HGNC: 18540] ENSG00000169344 UMDD HGNC Symbol uromodulin [Source: HGNC −0.76971558 0.181197865 Symbol; Acc: HGNC: 12559] ENSG00000169436 COL22A1 HGNC Symbol collagen type XXII alpha 1 chain −0.374497855 0.528626826 [Source: HGNC Symbol; Acc: HGNC: 22989] ENSG00000169862 CTNND2 HGNC Symbol catenin delta 2 [Source: HGNC −0.350904798 0.520102355 Symbol; Acc: HGNC: 2516] ENSG00000169876 MUC17 HGNC Symbol “mucin 17, cell −0.566443746 0.387767501 surface associated [Source: HGNC Symbol; Acc: HGNC: 16800]” ENSG00000170381 SEMA3E HGNC Symbol semaphorin 3E [Source: HGNC −0.598736051 0.385408727 Symbol; Acc: HGNC: 10727] ENSG00000170426 SDR9C7 HGNC Symbol short chain dehydragenase/ −0.869641519 0.163679446 reductase family 9C member 7 [Source: HGNC Symbol; Acc: HGNC: 29958] ENSG00000170442 KRT86 HGNC Symbol keratin 86 [Source: HGNC −0.370773529 0.370892028 Symbol; Acc: HGNC: 6463] ENSG00000170703 TTLL6 HGNC Symbol tubulin tyrosine ligase like 6 −0.589944567 0.344781215 [Source: HGNC Symbol; Acc: HGNC: 26664] ENSG00000170777 TPD52L3 HGNC Symbol tumor protein D52 like −0.585215371 0.382906193 3 [Source: HGNC Symbol; Acc: HGNC: 23382] ENSG00000170927 PKHD1 HGNC Symbol “PKHD1, fibrocystin/polyductin −0.246967015 0.708015783 [Source: HGNC Symbol; Acc: HGNC: 9016]” ENSG00000171435 KSR2 HGNC Symbol kinase suppressor of −0.428105876 0.450661319 ras 2 [Source: HGNC Symbol; Acc: HGNC: 18610] ENSG00000171487 NLRP5 HGNC Symbol NLR family pyrin domain containing 5 −0.238462882 0.710453093 [Source: HGNC Symbol; Acc: HGNC: 21269] ENSG00000171533 MAP6 HGNC Symbol microtubule associated protein G −0.731727753 0.156310461 [Source: HGNC Symbol; Acc: HGNC: 6868] ENSG00000171564 FGB HGNC Symbol fibrinogen beta chain [Source: HGNC −0.538885417 0.363987255 Symbol; Acc: HGNC: 3662] ENSG00000171587 DSCAM HGNC Symbol DS cell adhesion molecule −0.379128207 0.536270648 [Source: HGNC Symbol; Acc: HGNC: 3039] ENSG00000171804 WDR87 HGNC Symbol WD repeat domain 87 [Source: HGNC −0.521912283 0.382145668 Symbol; Acc: HGNC: 29934] ENSG00000172137 CALB2 HGNC Symbol calbindin 2 [Source: HGNC −0.440233971 0.434741137 Symbol; Acc: HGNC: 1435] ENSG00000172350 ABCG4 HGNC Symbol ATP binding cassette −0.409715093 0.501052173 subfamily G member 4 [Source: HGNC Symbol; Acc: HGNC: 13884] ENSG00000172752 COL6A5 HGNC Symbol collagen type VI alpha 5 chain −0.36150757 0.544869606 [Source: HGNC Symbol; Acc: HGNC: 26674] ENSG00000172900 AP002387.1 Clone-based −0.667266117 0.284084703 (Ensembl) gene ENSG00000172995 ARPP21 HGNC Symbol cAMP regulated phosphoprotein 21 −0.416436637 0.360871156 [Source: HGNC Symbol; Acc: HGNC: 16968] ENSG00000173013 CCDC96 HGNC Symbol coiled-coil domain containing 96 −0.507224369 0.111947151 [Source: HGNC Symbol; Acc: HGNC: 26900] ENSG00000173227 SYT12 HGNC Symbol synaptotagmin 12 [Source: HGNC −0.752963578 0.176041345 Symbol; Acc: HGNC: 18381] ENSG00000173572 NLRP13 HGNC Symbol NLR family pyrin −0.337498608 0.604591273 domain containing 13 [Source: HGNC Symbol; Acc: HGNC: 22937] ENSG00000173702 MUC13 HGNC Symbol “mucin 13, cell surface associated −0.770938778 0.184683607 [Source: HGNC Symbol; Acc: HGNC: 7511]” ENSG00000173769 TOPAZ1 HGNC Symbol testis and ovary specific −0.581049747 0.337975386 PAZ domain containing 1 [Source: HGNC Symbol; Acc: HGNC: 24746] ENSG00000173826 KCNH6 HGNC Symbol potassium voltage-gated −0.668262944 0.228310769 channel subfamily H member 6 [Source: HGNC Symbol; Acc: HGNC: 18862] ENSG00000174279 EVX2 HGNC Symbol even-skipped homeobox −0.532607087 0.366352883 2 [Source: HGNC Symbol; Acc: HGNC: 3507] ENSG00000174358 SLC6A19 HGNC Symbol solute carrier family G member 19 −0.552428142 0.229701299 [Source: HGNC Symbol; Acc: HGNC: 27960] ENSG00000174498 IGDCC3 HGNC Symbol immunoglobulin superfamily −0.500416529 0.386556 DCC subclass member 3 [Source: HGNC Symbol; Acc: HGNC: 9700] ENSG00000174502 SLC26A9 HGNC Symbol solute carrier family 26 member 9 −0.707160365 0.159137172 [Source: HGNC Symbol; Acc: HGNC: 14469] ENSG00000174963 ZIC4 HGNC Symbol Zic family member 4 [Source: HGNC −0.741912248 0.199304778 Symbol; Acc: HGNC: 20393] ENSG00000175084 DES HGNC Symbol desmin [Source: HGNC Symbol; −0.74969534 0.040474867 Acc: HGNC: 2770] ENSG00000175267 VWA3A HGNC Symbol von Willebrand factor A −0.713694352 0.037008563 domain containing 3A [Source: HGNC Symbol; Acc: HGNC: 27088] ENSG00000175267 VWA3A HGNC Symbol von Willebrand factor A −0.713694352 0.037008563 domain containing 3A [Source: HGNC Symbol; Acc: HGNC: 27088] ENSG00000175329 ISX HGNC Symbol intestine specific homeobox −0.48812621 0.42503419 [Source: HGNC Symbol; Acc: HGNC: 28084] ENSG00000175535 PNLIP HGNC Symbol pancreatic lipase [Source: HGNC −0.830503663 0.166474844 Symbol; Acc: HGNC: 9155] ENSG00000176584 DMBT1P1 HGNC Symbol deleted in malignant brain −0.301771252 0.660657448 tumors 1 pseudogene 1 [Source: HGNC Symbol; Acc: HGNC: 49497] ENSG00000176769 TCERG1L HGNC Symbol transcription elongation −0.433973597 0.471307255 regulator 1 like [Source: HGNC Symbol; Acc: HGNC: 23533] ENSG00000177045 SIX5 HGNC Symbol SIX homeobox 5 [Source: HGNC −0.498221295 0.307541999 Symbol; Acc: HGNC: 10891] ENSG00000177103 DSCAML1 HGNC Symbol DS cell adhesion molecule like 1 −0.501025251 0.288065754 [Source: HGNC Symbol; Acc: HGNC: 14656] ENSG00000177354 C10orf71 HGNC Symbol chromosome 10 open reading frame 71 −0.437224218 0.462998721 [Source: HGNC Symbol; Acc: HGNC: 26973] ENSG00000177511 ST8SIA3 HGNC Symbol “ST8 alpha-N-acetyl-neuraminide −0.634752306 0.292333593 alpha-2,8-sialyltransferase 3 [Source: HGNC Symbol; Acc: HGNC: 14269]” ENSG00000177551 NHLH2 HGNC Symbol nescient helix-loop-helix −0.492445704 0.413985661 2 [Source: HGNC Symbol; Acc: HGNC: 7818] ENSG00000178031 ADAMTSL1 HGNC Symbol ADAMTS like 1 [Source: HGNC −0.351255676 0.529035355 Symbol; Acc: HGNC: 14632] ENSG00000178171 AMER3 HGNC Symbol APC membrane recruitment protein 3 −0.457777165 0.432259224 [Source: HGNC Symbol; Acc: HGNC: 26771] ENSG00000178568 ERBB4 HGNC Symbol erb-b2 receptor tyrosine kinase 4 −0.165545558 0.837547319 [Source: HGNC Symbol; Acc: HGNC: 3432] ENSG00000178645 C10orf53 HGNC Symbol chromosome 10 open reading frame 53 −0.503971682 0.476649736 [Source: HGNC Symbol; Acc: HGNC: 27421] ENSG00000178965 ERICH3 HGNC Symbol glutamate rich 3 [Source: HGNC −0.468692004 0.391350792 Symbol; Acc: HGNC: 25346] ENSG00000179008 C14orf39 HGNC Symbol chromosome 14 open reading frame 39 −0.402370572 0.557284045 [Source: HGNC Symbol; Acc: HGNC: 19849] ENSG00000179178 TMEM125 HGNC Symbol transmembrane protein −0.507984532 0.427803498 125 [Source: HGNC Symbol; Acc: HGNC: 28275] ENSG00000179270 C2orf71 HGNC Symbol chromosome 2 open reading frame 71 −0.18942048 0.758600189 [Source: HGNC Symbol; Acc: HGNC: 34383] ENSG00000179709 NLRP8 HGNC Symbol NLR family pyrin −0.380100885 0.555880858 domain containing 8 [Source: HGNC Symbol; Acc: HGNC: 22940] ENSG00000179766 ATP8B5P HGNC Symbol “ATPase phospholipid −1.080551014 0.010971767 transporting 8B5, pseudogene [Source: HGNC Symbol; Acc: HGNC: 27245]” ENSG00000179813 FAM216B HGNC Symbol family with sequence −0.305849787 0.706075351 similarity 216 member B [Source: HGNC Symbol; Acc: HGNC: 26883] ENSG00000180251 SLC9A4 HGNC Symbol solute carrier family 9 member A4 −0.349423486 0.580620411 [Source: HGNC Symbol; Acc: HGNC: 11077] ENSG00000181143 MUC16 HGNC Symbol “mucin 16, cell −0.329348592 0.430361664 surface associated [Source: HGNC Symbol; Acc: HGNC: 15582]” ENSG00000181355 DFCC1 HGNC Symbol orofacial cleft 1 candidate −0.532362428 0.437641901 1 [Source: HGNC Symbol; Acc: HGNC: 21017] ENSG00000181378 CFAP65 HGNC Symbol cilia and flagella associated −0.434847926 0.442646097 protein 65 [Source: HGNC Symbol; Acc: HGNC: 25325] ENSG00000182256 GABRG3 HGNC Symbol gamma-aminobutyric −0.256293297 0.696478261 acid type A receptor gamma3 subunit [Source: HGNC Symbol; Acc: HGNC: 4088] ENSG00000183016 NA NA NA −0.30865823 0.660441616 ENSG00000183067 IGSF5 HGNC Symbol immunoglobulin superfamily member 5 −0.51302971 0.457242584 [Source: HGNC Symbol; Acc: HGNC: 5952] ENSG00000183206 POTEC HGNC Symbol POTE ankyrin domain family member C −0.327817046 0.614566385 [Source: HGNC Symbol; Acc: HGNC: 33894] ENSG00000183242 WT1-AS HGNC Symbol WT1 antisense RNA [Source: HGNC −0.327487007 0.63530305 Symbol; Acc: HGNC: 18135] ENSG00000183287 CCBE1 HGNC Symbol collagen and calcium binding −0.590879294 0.238072641 EGF domains 1 [Source: HGNC Symbol; Acc: HGNC: 29426] ENSG00000183304 FAM9A HGNC Symbol family with sequence −0.938058237 0.096563675 similarity 9 member A [Source: HGNC Symbol; Acc: HGNC: 18403] ENSG00000183317 EPHA10 HGNC Symbol EPH receptor A10 [Source: HGNC −0.469692297 0.372911095 Symbol; Acc: HGNC: 19987] ENSG00000183580 FBXL7 HGNC Symbol F-box and leucine rich −0.591833997 0.365077842 repeat protein 7 [Source: HGNC Symbol; Acc: HGNC: 13604] ENSG00000183668 PSG9 HGNC Symbol pregnancy specific −0.781212682 0.219746846 bata-1-glycoprotein 9 [Source: HGNC Symbol; Acc: HGNC: 9526] ENSG00000183778 B3GALT5 HGNC Symbol “bata-1,3- −0.49369755 0.401927772 galactosyltransfarase 5 [Source: HGNC Symbol; Acc: HGNC: 920]” ENSG00000183780 SLC35F3 HGNC Symbol solute carrier family 35 member F3 −0.289076693 0.422151105 [Source: HGNC Symbol; Acc: HGNC: 23616] ENSG00000183856 IQGAP3 HGNC Symbol IQ motif containing GTPase −0.465335464 0.302087891 activating protein 3 [Source: HGNC Symbol; Acc: HGNC: 20669] ENSG00000183876 ARS1 HGNC Symbol arylsulfatase family member 1 −0.487563606 0.409216161 [Source: HGNC Symbol; Acc: HGNC: 32521] ENSG00000183908 LRRC55 HGNC Symbol leucine rich repeat containing 55 −0.306233165 0.604776413 [Source: HGNC Symbol; Acc: HGNC: 32324] ENSG00000184012 TMPRSS2 HGNC Symbol transmembrane serine protease 2 −0.918034548 0.037008563 [Source: HGNC Symbol; Acc: HGNC: 11876] ENSG00000184227 ACOT1 HGNC Symbol acyl-CoA thioesterase −0.665299244 0.162555375 1 [Source: HGNC Symbol; Acc: HGNC: 33128] ENSG00000184302 SIX6 HGNC Symbol SIX homeobox 6 [Source: HGNC −0.504088891 0.441451067 Symbol; Acc: HGNC: 10892] ENSG00000184304 PRKD1 HGNC Symbol protein kinase D1 [Source: HGNC −0.428587371 0.415595988 Symbol; Acc: HGNC: 9407] ENSG00000184809 B3GALT5-AS1 HGNC Symbol B3GALT5 antisense −0.338454269 0.614566385 RNA1 [Source: HGNC Symbol; Acc: HGNC: 16424] ENSG00000184908 CLCNKB HGNC Symbol chloride voltage-gated channel Kb −0.357681839 0.540451079 [Source: HGNC Symbol; Acc: HGNC: 2027] ENSG00000185038 MRDH2A HGNC Symbol maestro heat like repeat −0.38431913 0.523839641 family member 2A [Source: HGNC Symbol; Acc: HGNC: 27936] ENSG00000185069 KRT7B HGNC Symbol keratin 76 [Source: HGNC −0.5580061 0.363389835 Symbol; Acc: HGNC: 24430] ENSG00000185303 SFTPA2 HGNC Symbol surfactant protein −0.803359583 0.189636469 A2 [Source: HGNC Symbol; Acc: HGNC: 10799] ENSG00000185313 SCN10A HGNC Symbol sodium voltage-gated channel −0.230551689 0.73625037 alpha subunit 10 [Source: HGNC Symbol; Acc: HGNC: 10582] ENSG00000185467 KPNA7 HGNC Symbol karyapherin subunit alpha −0.199440359 0.827997131 7 [Source: HGNC Symbol; Acc: HGNC: 21839] ENSG00000185686 PRAME HGNC Symbol preferentially expressed −0.683189263 0.231379249 antigen in melanome [Source: HGNC Symbol; Acc: HGNC: 9336] ENSG00000185737 NRG3 HGNC Symbol neuregulin 3 [Source: HGNC −0.331707231 0.60838718 Symbol; Acc: HGNC: 7999] ENSG00000185739 SRL HGNC Symbol sarcalumenin [Source: HGNC −0.778970248 0.182933474 Symbol; Acc: HGNC: 11295] ENSG00000185823 NPAP1 HGNC Symbol nuclear pore associated protein 1 −0.709460544 0.239778807 [Source: HGNC Symbol; Acc: HGNC: 1190] ENSG00000185974 GRK1 HGNC Symbol G protein-coupled receptor kinase 1 −0.524927614 0.365633153 [Source: HGNC Symbol; Acc: HGNC: 10013] ENSG00000186185 KIF18B HGNC Symbol kinesin family member −0.533902601 0.08735537 18B [Source: HGNC Symbol; Acc: HGNC: 27102] ENSG00000186393 KRT2G HGNC Symbol keratin 26 [Source: HGNC −0.510960904 0.393531656 Symbol; Acc: HGNC: 30840] ENSG00000186487 MYT1L HGNC Symbol myelin transcription factor 1 like −0.551259753 0.323477526 [Source: HGNC Symbol; Acc: HGNC: 7623] ENSG00000186526 CYP4F8 HGNC Symbol cytochrome P450 family 4 −0.633956341 0.284297086 subfamily F member 8 [Source: HGNC Symbol; Acc: HGNC: 2648] ENSG00000186862 PDZD7 HGNC Symbol PDZ domain containing −0.554675047 0.164105126 7 [Source: HGNC Symbol; Acc: HGNC: 26257] ENSG00000187068 C3orf70 HGNC Symbol chromosome 3 open −0.188322704 0.736814103 reading frame 70 [Source: HGNC Symbol; Acc: HGNC: 33731] ENSG00000187094 DDK HGNC Symbol cholecystokinin [Source: HGNC −0.809919388 0.141982169 Symbol; Acc: HGNC: 1569] ENSG00000187123 LYPDG HGNC Symbol LYG/PLAUR domain containing 6 −0.509808838 0.401011395 [Source: HGNC Symbol; Acc: HGNC: 28751] ENSG00000187527 ATP13A5 HGNC Symbol ATPase 13A5 [Source: HGNC −0.467545909 0.428173196 Symbol; Acc: HGNC: 31789] ENSG00000187772 LIN28B HGNC Symbol lin-28 homolog B [Source: HGNC −0.23447087 0.763770257 Symbol; Acc: HGNC: 32207] ENSG00000187905 LRRC74B HGNC Symbol leucine rich repeat containing 74B −0.461043362 0.41745351 [Source: HGNC Symbol; Acc: HGNC: 34301] ENSG00000187955 COL14A1 HGNC Symbol collagen type XIV alpha 1 chain −0.802642614 0.060883822 [Source: HGNC Symbol; Acc: HGNC: 2191] ENSG00000187997 C17orf99 HGNC Symbol chromosome 17 open reading frame 99 −0.54593757 0.228439083 [Source: HGNC Symbol; Acc: HGNC: 34490] ENSG00000188086 PRSS45 HGNC Symbol serine protease 45 [Source: HGNC −0.561060502 0.385562603 Symbol; Acc: HGNC: 30717] ENSG00000188112 C6orf132 HGNC Symbol chromosome 6 open reading frame 132 −0.912928908 0.01832644 [Source: HGNC Symbol; Acc: HGNC: 21288] ENSG00000188162 OTOG HGNC Symbol otogelin [Source: HGNC Symbol; −0.501929759 0.346681837 Acc: HGNC: 8516] ENSG00000188338 SLC38A3 HGNC Symbol solute carrier family 38 member 3 −0.761738167 0.152208524 [Source: HGNC Symbol; Acc: HGNC: 18044] ENSG00000188488 SERPINA5 HGNC Symbol serpin family A member −0.692734776 0.249894109 5 [Source: HGNC Symbol; Acc: HGNC: 8723] ENSG00000188706 ZDHHC9 HGNC Symbol zinc finger DHHC-type containing 9 −0.385110334 0.030930967 [Source: HGNC Symbol; Acc: HGNC: 18475] ENSG00000188782 DATSPER4 HGNC Symbol cation channel sperm associated 4 −0.829398746 0.157963233 [Source: HGNC Symbol; Acc: HGNC: 23220] ENSG00000188803 SHISA6 HGNC Symbol shisa family member 6 [Source: HGNC −0.516219657 0.41821783 Symbol; Acc: HGNC: 34491] ENSG00000188886 ASTL HGNC Symbol astacin like metalloendopeptidase −1.137626195 0.005079261 [Source: HGNC Symbol; Acc: HGNC: 31704] ENSG00000196091 MYBPD1 HGNC Symbol “myosin binding protein −0.430673258 0.437393542 C, slow type [Source: HGNC Symbol; Acc: HGNC: 7549]” ENSG00000196136 SERPINA3 HGNC Symbol serpin family A member −0.909069758 0.106147674 3 [Source: HGNC Symbol; Acc: HGNC: 16] ENSG00000196361 ELAVL3 HGNC Symbol ELAV like RNA binding protein 3 −0.75893849 0.141285189 [Source: HGNC Symbol; Acc: HGNC: 3314] ENSG00000196415 PRTN3 HGNC Symbol proteinase 3 [Source: HGNC −1.443754633 0.002256568 Symbol; Acc: HGNC: 9495] ENSG00000196565 HBG2 HGNC Symbol hemoglobin subunit gamma −0.931424276 0.014195699 2 [Source: HGNC Symbol; Acc: HGNC: 4832] ENSG00000196862 RGPD4 HGNC Symbol RANBP2-like and GRIP −0.694081274 0.03331637 domain containing 4 [Source: HGNC Symbol; Acc: HGNC: 32417] ENSG00000197079 KRT35 HGNC Symbol keratin 35 [Source: HGNC −0.658605324 0.248428762 Symbol; Acc: HGNC: 6453] ENSG00000197085 NPSR1-AS1 HGNC Symbol NPSR1 antisense RNA −0.47682751 0.385383626 1 [Source: HGNC Symbol; Acc: HGNC: 22128] ENSG00000197406 DIO3 HGNC Symbol iodothyronine deiodinase −0.582483697 0.278225713 3 [Source: HGNC Symbol; Acc: HGNC: 2885] ENSG00000197408 CYP2BG HGNC Symbol cytochrome P450 family 2 −0.59980912 0.385010224 subfamily B member 6 [Source: HGNC Symbol; Acc: HGNC: 2615] ENSG00000197893 NRAP HGNC Symbol neublin related anchoring protein −0.32566366 0.63782084 [Source: HGNC Symbol; Acc: HGNC: 7988] ENSG00000197991 AL592490.1 Clone-based −0.605428219 0.343100516 (Ensembl) gene ENSG00000198010 DLGAP2 HGNC Symbol DLG associated protein −0.462914925 0.409741714 2 [Source: HGNC Symbol; Acc: HGNC: 2906] ENSG00000198597 ZNF536 HGNC Symbol zinc finger protein −0.318101569 0.612448109 536 [Source: HGNC Symbol; Acc: HGNC: 29025] ENSG00000198765 SYCP1 HGNC Symbol synaptonemal complex −0.4742583 0.465583509 protein 1 [Source: HGNC Symbol; Acc: HGNC: 11487] ENSG00000198788 MUC2 HGNC Symbol “mucin 2, oligomeric −0.356584229 0.524732504 mucus/gel-forming [Source: HGNC Symbol; Acc: HGNC: 7512]” ENSG00000198914 POU3F3 HGNC Symbol POU class 3 homeobox −0.566373551 0.326225195 3 [Source: HGNC Symbol; Acc: HGNC: 9216] ENSG00000198929 NDS1AP HGNC Symbol citric oxide synthase −0.522447538 0.23360559 1 adaptor protein [Source: HGNC Symbol; Acc: HGNC: 16859] ENSG00000203805 PLPP4 HGNC Symbol phospholipid phosphatase −0.645867767 0.226621278 4 [Source: HGNC Symbol; Acc: HGNC: 23531] ENSG00000203900 AL121827.1 Clone-based −0.907580244 0.056158339 (Ensembl) gene ENSG00000204055 AL158151.1 Clone-based −0.30965968 0.531561049 (Ensembl) gene ENSG00000204241 AP000911.1 Clone-based −0.524122921 0.047699169 (Ensembl) gene ENSG00000204283 LINC01973 HGNC Symbol long intergenic non-protein −0.688310921 0.054758157 coding RNA 1973 [Source: HGNC Symbol; Acc: HGNC: 52800] ENSG00000204335 SP5 HGNC Symbol Sp5 transcription factor −0.781301125 0.179308229 [Source: HGNC Symbol; Acc: HGNC: 14529] ENSG00000204624 DISP3 HGNC Symbol dispatched RND transporter −0.556015174 0.112163059 family member 3 [Source: HGNC Symbol; Acc: HGNC: 29251] ENSG00000204661 C5orf60 HGNC Symbol chromosome 5 open reading frame 60 −0.728340381 0.247590568 [Source: HGNC Symbol; Acc: HGNC: 27753] ENSG00000204929 AC007389.1 Clone-based −0.641685442 0.282661756 (Ensembl) gene ENSG00000204941 PSG5 HGNC Symbol pregnancy specific −0.381745193 0.571961572 beta-1-glycoprotein 5 [Source: HGNC Symbol; Acc: HGNC: 9522] ENSG00000205054 LINC01121 HGNC Symbol long intergenic non-protein −0.287245288 0.691210517 coding RNA 1121 [Source: HGNC Symbol; Acc: HGNC: 49266] ENSG00000205176 REXD1L1P HGNC Symbol “REXD1 like 1, pseudogene −0.633446822 0.361284725 [Source: HGNC Symbol; Acc: HGNC: 24660]” ENSG00000205312 KRT17P4 HGNC Symbol keratin 17 pseudogene −0.714632356 0.27010304 4 [Source: HGNC Symbol; Acc: HGNC: 50722] ENSG00000205396 LINC00661 HGNC Symbol long intergenic non-protein −0.690084698 0.181892869 coding RNA 661 [Source: HGNC Symbol; Acc: HGNC: 27002] ENSG00000205592 MUC19 HGNC Symbol “mucin 19, oligomeric −0.306611845 0.552328817 [Source: HGNC Symbol; Acc: HGNC: 14362]” ENSG00000205667 ARSH HGNC Symbol arylsulfatase family −0.537595932 0.388904138 member H [Source: HGNC Symbol; Acc: HGNC: 32488] ENSG00000205922 DNECUT3 HGNC Symbol one cut homeobox 3 [Source: HGNC −0.673541588 0.251060423 Symbol; Acc: HGNC: 13399] ENSG00000205976 AC091951.1 Clone-based −0.72127846 0.22466354 (Ensembl) gene ENSG00000210127 MT-TA HGNC Symbol mitochoodrially encoded −0.730149542 0.078668046 tRNA alanine [Source: HGNC Symbol; Acc: HGNC: 7475] ENSG00000213467 HMGB1P37 HGNC Symbol high mobility group box −1.143333307 0.002787608 1 pseudogene 37 [Source: HGNC Symbol; Acc: HGNC: 39184] ENSG00000213864 EEF1B2P2 HGNC Symbol eukaryotic translation elongation −1.164370093 0.00450201 factor 1 beta 2 pseudogene 2 [Source: HGNC Symbol; Acc: HGNC: 3209] ENSG00000213934 HBG1 HGNC Symbol hemoglobin subunit −1.506132934 0.001753409 gamma 1 [Source: HGNC Symbol; Acc: HGNC: 4831] ENSG00000214128 TMEM213 HGNC Symbol transmembrane protein −0.721138795 0.190125378 213 [Source: HGNC Symbol; Acc: HGNC: 27220] ENSG00000214181 NA NA NA −0.970789027 0.013222867 ENSG00000214402 LCNL1 HGNC Symbol lipocalin like 1 [Source: HGNC −0.706465394 0.073719528 Symbol; Acc: HGNC: 34436] ENSG00000214929 SPATA31D1 HGNC Symbol SPATA31 subfamily D −0.65113278 0.36620383 member 1 [Source: HGNC Symbol; Acc: HGNC: 37283] ENSG00000215405 NA NA NA −0.617865475 0.352456865 ENSG00000215864 NBPF7 HGNC Symbol NBPF member 7 [Source: HGNC −0.90843358 0.018653866 Symbol; Acc: HGNC: 31989] ENSG00000215895 AL354702.1 Clone-based −0.782838755 0.075685055 (Ensembl) gene ENSG00000217094 PPIAP31 HGNC Symbol peptidylprolyl isomerase −0.998868816 0.000348277 A pseudogene 31 [Source: HGNC Symbol; Acc: HGNC: 44962] ENSG00000218586 AC006971.1 Clone-based −0.955494818 0.015850348 (Ensembl) gene ENSG00000218672 AC008060.1 Clone-based −0.770845732 0.19404204 (Ensembl) gene ENSG00000218823 PAPOLB HGNC Symbol poly(A) polymerase −0.719493482 0.27787686 beta [Source: HGNC Symbol; Acc: HGNC: 15970] ENSG00000221826 PSG3 HGNC Symbol pregnancy specific −0.240003956 0.750637339 beta-1-glycoprotein 3 [Source: HGNC Symbol; Acc: HGNC: 9520] ENSG00000221878 PSG7 HGNC Symbol pregnancy specific −0.453292662 0.540259029 beta-1-glycoprotein 7 (gene/pseudogene) [Source: HGNC Symbol; Acc: HGNC: 9524] ENSG00000223414 LINC00473 HGNC Symbol long intergenic non-protein −1.017484945 0.084276877 coding RNA 473 [Source: HGNC Symbol; Acc: HGNC: 21160] ENSG00000223566 TNRC18P2 HGNC Symbol trinucleotide repeat −0.653114849 0.205565205 containing 18 pseudogene 2 [Source: HGNC Symbol; Acc: HGNC: 34014] ENSG00000223949 ROR1-AS1 HGNC Symbol ROR1 antisense RNA −0.645751328 0.290941527 1 [Source: HGNC Symbol; Acc: HGNC: 40508] ENSG00000224059 HSPA8P16 HGNC Symbol heat shock protein family −1.139741884 0.026824728 A (Hsp70) member 8 pseudogene 16 [Source: HGNC Symbol; Acc: HGNC: 44931] ENSG00000224209 LINC00466 HGNC Symbol long intergenic non-protein −1.176248621 0.039820431 coding RNA 466 [Source: HGNC Symbol; Acc: HGNC: 27294] ENSG00000224271 AL117329.1 Clone-based −0.663993539 0.277648202 (Ensembl) gene ENSG00000224367 OACYLP HGNC Symbol “O-acyltransferase −0.608155491 0.296095547 like, pseudogene [Source: HGNC Symbol; Acc: HGNC: 44362]” ENSG00000224435 NF1P6 HGNC Symbol neurofibromin 1 pseudogene −0.892662927 0.117501042 6 [Source: HGNC Symbol; Acc: HGNC: 7771] ENSG00000224668 IPD8P1 HGNC Symbol importin 8 pseudogene −0.694695462 0.099383688 1 [Source: HGNC Symbol; Acc: HGNC: 41955] ENSG00000224743 TEX26-AS1 HGNC Symbol TEX26 anitsense RNA −0.60820906 0.280832206 1 [Source: HGNC Symbol; Acc: HGNC: 42784] ENSG00000225637 AP001046.1 Clone-based −0.681940896 0.281192155 (Ensembl) gene ENSG00000225649 AC064875.1 Clone-based −0.698790548 0.326326486 (Ensembl) gene ENSG00000225813 AC009299.1 Clone-based −0.210665195 0.744296595 (Ensembl) gene ENSG00000225953 SATB2-AS1 HGNC Symbol SATB2 antisense RNA −0.527452078 0.302412079 1 [Source: HGNC Symbol; Acc: HGNC: 26490] ENSG00000226057 PHF2P2 HGNC Symbol PHD finger protein 2 pseudogene 2 −0.337369658 0.356815552 [Source: HGNC Symbol; Acc: HGNC: 38808] ENSG00000226068 HNRNPA3P4 HGNC Symbol heterogeneous nuclear −1.120089183 0.013553682 ribonucleoprotein A3 pseudogene 4 [Source: HGNC Symbol; Acc: HGNC: 39773] ENSG00000226440 AL365214.2 Clone-based −0.699415602 0.287780065 (Ensembl) gene ENSG00000226741 LINC02554 HGNC Symbol long intergenic −0.684878038 0.273326765 non-coding RNA 2554 [Source: HGNC Symbol; Acc: HGNC: 53594] ENSG00000226790 HNRNPA3P1 HGNC Symbol heterogeneous nuclear −1.384734034 0.000189579 ribonucleoprotein A3 pseudogene 1 [Source: HGNC Symbol; Acc: HGNC: 13729] ENSG00000227036 LINC00511 HGNC Symbol long intergenic non-protein −0.508830938 0.153757922 coding RNA 511 [Source: HGNC Symbol; Acc: HGNC: 43564] ENSG00000227471 AKR1B15 HGNC Symbol aldo-keto reductase family −0.827071435 0.171395362 1 member B15 [Source: HGNC Symbol; Acc: HGNC: 37281] ENSG00000227525 RPL7P6 HGNC Symbol ribosomal protein L7 pseudogene 6 −1.209818266 0.003030406 [Source: HGNC Symbol; Acc: HGNC: 32430] ENSG00000227744 LINC01940 HGNC Symbol long intergenic non-protein −0.606198906 0.304426384 coding RNA 1940 [Source: HGNC Symbol; Acc: HGNC: 52763] ENSG00000227827 AC138969.2 Clone-based −0.592806597 0.166783813 (Ensembl) gene ENSG00000228549 BX284668.2 Clone-based −0.68006559 0.067244282 (Ensembl) gene ENSG00000228983 SLC47A1P1 HGNC Symbol solute carrier family 47 −0.809148556 0.2081298 member 1 pseudogene 1 [Source: HGNC Symbol; Acc: HGNC: 51849] ENSG00000229147 SMPD4P2 HGNC Symbol sphingomyelin phosphodiesterase −0.546120346 0.368203078 4 pseudogene 2 [Source: HGNC Symbol; Acc: HGNC: 39674] ENSG00000229240 LINC00710 HGNC Symbol long intergenic non-protein −0.349696304 0.636769038 coding RNA 710 [Source: HGNC Symbol; Acc: HGNC: 27386] ENSG00000229817 AL133412.1 Clone-based −1.134095271 0.031106855 (Ensembl) gene ENSG00000229972 IQCF3 HGNC Symbol IQ motif containing −0.707465438 0.238864276 F3 [Source: HGNC Symbol; Acc: HGNC: 31816] ENSG00000230102 LINC0208 HGNC Symbol long intergenic non-protein −0.84996372 0.156994187 coding RNA 2028 [Source: HGNC Symbol; Acc: HGNC: 27718] ENSG00000230133 LINC01721 HGNC Symbol long intergenic non-protein −0.269403043 0.711053504 coding RNA 1721 [Source: HGNC Symbol; Acc: HGNC: 52508] ENSG00000230392 AC004835.1 Clone-based −0.84709631 0.102864131 (Ensembl) gene ENSG00000230552 AC092162.2 Clone-based −0.369157666 0.571101565 (Ensembl) gene ENSG00000230615 AL139220.2 Clone-based −0.52204036 0.382207592 (Ensembl) gene ENSG00000230873 STMND1 HGNC Symbol stathmin domain containing −0.360296128 0.61243615 1 [Source: HGNC Symbol; Acc: HGNC: 44668] ENSG00000231131 LINC01468 HGNC Symbol long intergenic non-protein −0.539334563 0.42259164 coding RNA 1468 [Source: HGNC Symbol; Acc: HGNC: 50913] ENSG00000231422 LINC01516 HGNC Symbol long intergenic non-protein −0.556463466 0.39546555 coding RNA 1516 [Source: HGNC Symbol; Acc: HGNC: 51211] ENSG00000232392 AC002366.1 Clone-based −0.504607303 0.313754361 (Ensembl) gene ENSG00000232667 AC004862.1 Clone-based −0.377421732 0.617985726 (Ensembl) gene ENSG00000232756 AC004996.1 Clone-based −0.532711499 0.428875064 (Ensembl) gene ENSG00000233183 AL138889.1 Clone-based −0.644340746 0.293569058 (Ensembl) gene ENSG00000233395 LINC00841 HGNC Symbol long intergenic non-protein −0.755094485 0.24458117 coding RNA 841 [Source: HGNC Symbol; Acc: HGNC: 27430] ENSG00000233485 AL031283.2 Clone-based −0.639007269 0.295175271 (Ensembl) gene ENSG00000233539 AC011294.1 Clone-based −0.707276432 0.262329375 (Ensembl) gene ENSG00000233973 LINC01360 HGNC Symbol long intergenic non-protein −0.427339916 0.546690871 coding RNA 1360 [Source: HGNC Symbol; Acc: HGNC: 50593] ENSG00000233977 AC099681.3 Clone-based −1.209272617 0.027526442 (Ensembl) gene ENSG00000233991 NA NA NA −0.525516632 0.310266093 ENSG00000234130 AL359263.1 Clone-based −0.983040041 0.004471167 (Ensembl) gene ENSG00000234177 LINC01114 HGNC Symbol long intergenic non-protein −0.49846577 0.434856109 coding RNA 1114 [Source: HGNC Symbol; Acc: HGNC: 49245] ENSG00000234512 TLR12P HGNC Symbol “toll like receptor 12, pseudogene −0.514872503 0.441103354 [Source: HGNC Symbol; Acc: HGNC: 31754]” ENSG00000234537 AL354751.1 Clone-based −0.384649992 0.532855004 (Ensembl) gene ENSG00000234828 IQCM HGNC Symbol IQ motif containing −0.677274946 0.33050019 M [Source: HGNC Symbol; Acc: HGNC: 53443] ENSG00000235711 ANKRD34C HGNC Symbol ankyrin repeat domain −0.629664373 0.321694729 34C [Source: HGNC Symbol; Acc: HGNC: 33888] ENSG00000235881 AC114776.1 Clone-based −0.567508401 0.40045344 (Ensembl) gene ENSG00000236078 LINC01447 HGNC Symbol long intergenic non-protein −0.901815564 0.106966165 ending RNA 1447 [Source: HGNC Symbol; Acc: HGNC: 50783] ENSG00000236229 VEZF1P1 HGNC Symbol vascular endothelial zinc −0.741631818 0.120281894 finger 1 pseudogene 1 [Source: HGNC Symbol; Acc: HGNC: 32320] ENSG00000236253 SLC25A3P1 HGNC Symbol solute carrier family −0.817459523 0.156635614 25 member 3 pseudogene 1 [Source: HGNC Symbol; Acc: HGNC: 26869] ENSG00000236404 VLDLR-AS1 HGNC Symbol VLDLR antisense RNA −0.617831635 0.280386176 1 [Source: HGNC Symbol; Acc: HGNC: 49621] ENSG00000236445 LINC00608 HGNC Symbol long intergenic non-protein −0.743359785 0.28126695 coding RNA 608 [Source: HGNC Symbol; Acc: HGNC: 27179] ENSG00000236824 BCYRN1 HGNC Symbol brain cytoplasmic −0.656526317 0.083153215 RNA 1 [Source: HGNC Symbol; Acc: HGNC: 1022] ENSG00000237125 HAND2-AS1 HGNC Symbol HAND2 antisense RNA 1 −0.621343361 0.260507627 (head to head) [Source: HGNC Symbol; Acc: HGNC: 48872] ENSG00000237222 LINC01968 HGNC Symbol long intergenic non-protein −0.672454358 0.277770947 coding RNA 1968 [Source: HGNC Symbol; Acc: HGNC: 52794] ENSG00000237250 AL359924.1 Clone-based −0.844197088 0.255602335 (Ensembl) gene ENSG00000237289 CKMT1B HGNC Symbol “creatine kinase, −0.216490618 0.795077893 mitochondrial 1B [Source: HGNC Symbol; Acc: HGNC: 1995]” ENSG00000237390 AL139130.1 Clone-based −0.681458963 0.223257294 (Ensembl) gene ENSG00000237515 SHISA9 HGNC Symbol shisa family member −0.809010055 0.106410732 9 [Source: HGNC Symbol; Acc: HGNC: 37231] ENSG00000237636 ANKRD26P3 HGNC Symbol ankyrin repeat domain −0.387705186 0.561900253 26 pseudogene 3 [Source: HGNC Symbol; Acc: HGNC: 39689] ENSG00000238116 Z95327.1 Clone-based −1.006307186 0.058635061 (Ensembl) gene ENSG00000239921 LINC01471 HGNC Symbol long intergenic non-protein −0.433460557 0.515402598 coding RNA 1471 [Source: HGNC Symbol; Acc: HGNC: 51106] ENSG00000240021 TEX35 HGNC Symbol testis expressed −0.374999293 0.569064774 35 [Source: HGNC Symbol; Acc: HGNC: 25366] ENSG00000240694 PNMA2 HGNC Symbol PNMA family member −0.937890632 0.011844862 2 [Source: HGNC Symbol; Acc: HGNC: 9159] ENSG00000240707 LINC01168 HGNC Symbol long intergenic non-protein −0.843835897 0.086801762 coding RNA 1168 [Source: HGNC Symbol; Acc: HGNC: 49537] ENSG00000241158 ADAMTS9-AS1 HGNC Symbol ADAMTS9 antisense −0.408694485 0.583233437 RNA 1 [Source: HGNC Symbol; Acc: HGNC: 40625] ENSG00000242512 LINC01206 HGNC Symbol long intergenic non-protein −0.706615823 0.298614872 coding RNA 1206 [Source: HGNC Symbol; Acc: HGNC: 49637] ENSG00000242866 STRC HGNC Symbol stereocilin [Source: HGNC −0.378462607 0.423980174 Symbol; Acc: HGNC: 16035] ENSG00000243130 PSG11 HGNC Symbol pregnancy specific −0.64081905 0.353755564 beta-1-glycoprotein 11 [Source: HGNC Symbol; Acc: HGNC: 9516] ENSG00000244694 PTCHD4 HGNC Symbol patched domain containing −0.961630256 0.109326576 4 [Source: HGNC Symbol; Acc: HGNC: 21345] ENSG00000245248 USP2-AS1 HGNC Symbol DSP2 antisense RNA 1 (head to head) −0.520768111 0.390756877 [Source: HGNC Symbol; Acc: HGNC: 48673] ENSG00000245651 AC083805.1 Clone-based −0.541469632 0.389457898 (Ensembl) gene ENSG00000246695 RASSF8-AS1 HGNC Symbol RASSF8 antisense RNA −0.616821021 0.302209736 1 [Source: HGNC Symbol; Acc: HGNC: 48637] ENSG00000247213 LINC01498 HGNC Symbol long intergenic non-protein −0.955409024 0.107829748 coding RNA 1498 [Source: HGNC Symbol; Acc: HGNC: 51164] ENSG00000247699 AC008609.1 Clone-based −1.050990069 0.073837393 (Ensembl) gene ENSG00000248587 GDNF-AS1 HGNC Symbol GDNF antisense RNA 1 −0.698157573 0.21408791 (head to head) [Source: HGNC Symbol; Acc: HGNC: 43592] ENSG00000248713 AC083902.2 Clone-based “Homo sapiens −0.540713726 0.305645261 (Ensembl) gene uncharacterized LOC285556 (LOC285556), mRNA. [Source: RefSeq mRNA; Acc: NM_001354435]” ENSG00000248746 ACTN3 HGNC Symbol actinin alpha 3 (gene/pseudogene) −0.833558399 0.085185005 [Source: HGNC Symbol; Acc: HGNC: 165] ENSG00000248966 BCLAF1P1 HGNC Symbol BCL2 associated transcription factor 1 −0.901954794 0.005426121 pseudogene 1 [Source: HGNC Symbol; Acc: HGNC: 51329] ENSG00000248975 AL133372.2 Clone-based −0.655164585 0.316622442 (Ensembl) gene ENSG00000249119 MTNDGP4 HGNC Symbol mitochondrially encoded −1.255534276 0.007501713 NADH: ubiquinone oxidoreductase care subunit 6 pseudogene 4 [Source: HGNC Symbol; Acc: HGNC: 39467] ENSG00000249215 NCOA4P4 HGNC Symbol nuclear receptor coactivator −1.297109171 0.000137132 4 pseudogene 4 [Source: HGNC Symbol; Acc: HGNC: 52405] ENSG00000249267 LINC00939 HGNC Symbol long intergenic non-protein −0.755105061 0.228670526 coding RNA 939 [Source: HGNC Symbol; Acc: HGNC: 48631] ENSG00000249341 AC124017.1 Clone-based −0.838158018 0.180191435 (Ensembl) gene ENSG00000249464 LINC01091 HGNC Symbol long intergenic non-protein −0.927878847 0.088700609 coding RNA 1091 [Source: HGNC Symbol; Acc: HGNC: 27721] ENSG00000249584 LINC02225 HGNC Symbol long intergenic non-protein −0.580968221 0.346216369 coding RNA 2225 [Source: HGNC Symbol; Acc: HGNE: 53094] ENSG00000249618 LINC02465 HGNC Symbol long intergenic non-protein −0.994691738 0.119254417 coding RNA 2465 [Source: HGNC Symbol; Acc: HGNC: 53403] ENSG00000250049 AC114316.2 Clone-based −0.734378499 0.217922591 (Ensembl) gene ENSG00000250230 AP002754.1 Clone-based −1.010448463 0.076383023 (Ensembl) gene ENSG00000250420 AACSP1 HGNC Symbol acetoacetyl-CoA synthetase −0.85134176 0.138526408 pseudogene 1 [Source: HGNC Symbol; Acc: HGNC: 18226] ENSG00000250423 KIAA1210 HGNC Symbol KIAA1210 [Source: HGNC Symbol; −0.616623881 0.302589969 Acc: HGNC: 29218] ENSG00000250493 AP004147.1 Clone-based −0.423508937 0.487573965 (Ensembl) gene ENSG00000250519 AP002784.1 Clone-based −0.661885269 0.300298544 (Ensembl) gene ENSG00000250546 AC079160.1 Clone-based −0.594876334 0.407745799 (Ensembl) gene ENSG00000251557 HNRNPKP3 HGNC Symbol heterogenous nuclear −0.983325003 0.155739901 ribonucleoprotein K pseudogene 3 [Source: HGNC Symbol; Acc: HGNC: 42376] ENSG00000251596 HADHAP1 HGNC Symbol “hydroxyacyl-CoA −0.74139099 0.215412986 dehydrogenase/3-ketoacyl-CoA thiolase/enoyl-CoA hydratase (trifunctional protein), alpha subunit pseudogene 1 [Source: HGNC Symbol; Acc: HGNC: 4802]” ENSG00000251705 RNA5-8SP6 HGNC Symbol “RNA, 5.8S ribosomal pseudogene 6 −0.425991485 0.294278305 [Source: HGNC Symbol; Acc: HGNC: 41960]” ENSG00000253230 LINC00599 HGNC Symbol long intergenic non-protein −0.760456332 0.135076382 coding RNA 599 [Source: HGNC Symbol; Acc: HGNC: 27231] ENSG00000253288 AC046195.1 Clone-based −0.709937286 0.305188446 (Ensembl) gene ENSG00000253301 LINC01606 HGNC Symbol long intergenic non-protein −0.711369904 0.234542306 coding RNA 1606 [Source: HGNC Symbol; Acc: HGNC: 51656] ENSG00000253864 NA NA NA −0.889113296 0.11585236 ENSG00000253871 AC068075.1 Clone-based −1.11237045 0.076114677 (Ensembl) gene ENSG00000253974 NRG1-IT1 HGNC Symbol NRG1 intrunic transcript −0.501373766 0.471813581 1 [Source: HGNC Symbol; Acc: HGNC: 43633] ENSG00000254042 ACD11365.1 Clone-based −0.600224259 0.364960528 (Ensembl) gene ENSG00000254101 LINC02055 HGNC Symbol long intergenic non-protein −0.903549507 0.185220622 coding RNA 2055 [Source: HGNC Symbol; Acc: HGNC: 52895] ENSG00000254561 AP003393.1 Clone-based −0.734861559 0.197377124 (Ensembl) gene ENSG00000256343 AC095350.1 Clone-based −0.895023552 0.169037894 (Ensembl) gene ENSG00000256612 CYP2B7P HGNC Symbol “cytochrome P450 family −0.489134845 0.20391081 2 subfamily B member 7, pseudogene [Source: HGNC Symbol; Acc: HGNC: 2616]” ENSG00000256616 AP002414.2 Clone-based −0.533801034 0.439483446 (Ensembl) gene ENSG00000257008 GPR142 HGNC Symbol G protein-coupled receptor −0.88549094 0.103049732 142 [Source: HGNC Symbol; Acc: HGNC: 20088] ENSG00000257175 CR383656.1 Clone-based −0.641868034 0.142758994 (Ensembl) gene ENSG00000257576 HSPD1P4 HGNC Symbol heat shock prat Bin −0.870496882 0.027959144 family D (Hsp60) member 1 pseudogene 4 [Source: HGNC Symbol; Acc: HGNC: 35146] ENSG00000257907 EEF1A1P17 HGNC Symbol eukaryotic translation −1.061336051 0.012387251 elongation factor 1 alpha 1 pseudogene 17 [Source: HGNC Symbol; Acc: HGNC: 37890] ENSG00000258628 AC126603.1 Clone-based −0.496381087 0.388904138 (Ensembl) gene ENSG00000258679 AC121758.1 Clone-based −0.657256137 0.268271188 (Ensembl) gene ENSG00000259010 AL049869.1 Clone-based −1.06237153 0.004353922 (Ensembl) gene ENSG00000259156 CHEK2P2 HGNC Symbol checkpoint kinase 2 pseudogene −0.816062698 0.100260967 2 [Source: HGNC Symbol; Acc: HGNC: 43578] ENSG00000259176 NA NA NA −0.689122052 0.24300017 ENSG00000259380 AC087473.1 Clone-based −0.259518718 0.707119428 (Ensembl) gene ENSG00000259458 AC100839.1 Clone-based −0.711262016 0.226889647 (Ensembl) gene ENSG00000259790 ANP32BP1 HGNC Symbol acidic nuclear phosphoprotein −0.99159785 0.001291068 32 family member B pseudogene 1 [Source: HGNC Symbol; Acc: HGNC: 24267] ENSG00000259841 LINC01566 HGNC Symbol long intergenic non-protein −0.459757156 0.519499356 coding RNA 1566 [Source: HGNC Symbol; Acc: HGNC: 27555] ENSG00000260027 HOXB7 HGNC Symbol homeobox B7 [Source: HGNC −0.542434326 0.225372277 Symbol; Acc: HGNC: 5118] ENSG00000260072 AC008938.1 Clone-based −0.616696682 0.313465888 (Ensembl) gene ENSG00000260290 AC092115.1 Clone-based −0.846632607 0.001798958 (Ensembl) gene ENSG00000260305 NTRK3-AS1 HGNC Symbol NTRK3 antisense RNA −0.409045013 0.529909289 1 [Source: HGNC Symbol; Acc: HGNC: 27532] ENSG00000260411 NA NA NA −0.513027268 0.393639567 ENSG00000260759 AP001120.1 Clone-based −0.782720245 0.215023019 (Ensembl) gene ENSG00000261104 AC093904.4 Clone-based −0.334778367 0.600661825 (Ensembl) gene ENSG00000261115 TMEM178B HGNC Symbol transmembrane protein −0.352100285 0.265283771 178B [Source: HGNC Symbol; Acc: HGNC: 44112] ENSG00000261177 AC135012.1 Clone-based −0.994275816 0.048314645 (Ensembl) gene ENSG00000261275 AC092447.8 Clone-based −0.812472764 0.203816116 (Ensembl) gene ENSG00000261466 AC136944.4 Clone-based −1.109539774 0.041757833 (Ensembl) gene ENSG00000261623 LINC02179 HGNC Symbol long intergenic non-protein −0.11447084 0.908308893 coding RNA 2179 [Source: Symbol; Acc: HGNC: 53041] ENSG00000261649 GOLGA6L7 HGNC Symbol golgin A6 family like −1.108323245 0.018730492 7 [Source: HGNC Symbol; Acc: HGNC: 37442] ENSG00000261949 GFY HGNC Symbol golgi associated olfactory −0.815057864 0.178504736 signaling regulator [Source: HGNC Symbol; Acc: HGNC: 44663] ENSG00000262691 AC040160.1 Clone-based −0.536786924 0.387929026 (Ensembl) gene ENSG00000263711 AC079062.1 Clone-based −0.664230562 0.292210006 (Ensembl) gene ENSG00000264954 PRR29-AS1 HGNC Symbol PRR29 antisense RNA1 −0.735900318 0.102864131 [Source: HGNC Symbol; Acc: HGNC: 51822] ENSG00000265041 AC015688.3 Clone-based −0.765364276 0.178504736 (Ensembl) gene ENSG00000266172 NA NA NA −0.643514714 0.277770947 ENSG00000266795 NA NA NA −0.903848134 0.094040442 ENSG00000267324 AC006557.2 Clone-based −0.380979397 0.536886334 (Ensembl) gene ENSG00000268388 FENDRR HGNC Symbol FDXF1 adjacent non-coding −0.688358604 0.302352803 developmental regulatory RNA [Source: HGNC Symbol; Acc: HGNC: 43894] ENSG00000268460 AC006262.1 Clone-based −0.863478705 0.141982169 (Ensembl) gene ENSG00000269332 GOLGA2P9 HGNC Symbol golgin A2 pseudogene −0.795855321 0.179308229 9 (Source: HGNC Symbol; Acc: HGNC: 49921] ensembl p16.logFC p16.FDR p17.logFC p17.FDR p18.logFC p18.FDR ENSG00000002746 −0.328868097 1 0.438047831 0.908518526 0.257699857 1 ENSG00000004948 0.278685382 1 2.655446254 0.699814612 0.328026413 1 ENSG00000006071 −0.183143093 1 −0.151122062 0.972840456 0.060166206 1 ENSG00000006128 −0.42309878 1 −0.821588596 0.86142478 0.611538787 1 ENSG00000006210 0.394994483 1 0.142838907 0.984792321 −0.105867018 1 ENSG00000006283 −0.153595375 1 0.736365852 0.850152372 0.013389601 1 ENSG00000006788 −0.132296216 1 1.277263446 0.740349802 0.194022822 1 ENSG00000009709 −0.237365593 1 6.295166726 0.627668963 0.231942676 1 ENSG00000011677 −0.442276362 1 1.889252428 0.751835169 0.151297142 1 ENSG00000015520 −0.700785246 1 −0.349775321 0.929542543 0.193503425 1 ENSG00000018607 −0.226758688 1 0.349569946 0.959459365 0.583710154 1 ENSG00000018625 −0.323676225 1 1.616286887 0.721222226 0.112816854 1 ENSG00000019505 0.192851682 1 1.766660549 0.735101069 −0.059220871 1 ENSG00000039139 −0.350782091 1 0.33637337 0.929444622 0.374918338 1 ENSG00000039987 −0.266358455 1 −0.702991923 0.879866057 −0.349787212 1 ENSG00000054356 0.117493297 1 −0.428199871 0.839974197 −0.036044109 1 ENSG00000060656 −0.204609501 1 0.38533287 0.883612252 0.052221341 1 ENSG00000060709 −0.14886622 1 0.267280913 0.953466793 −0.023574473 1 ENSG00000068078 0.779778588 1 0.665950568 0.860481624 −0.338607178 1 ENSG00000069431 −0.698467209 1 1.501464862 0.754933936 0.427108144 1 ENSG00000070886 0.037142847 1 0.618792016 0.876857452 −0.131880882 1 ENSG00000072041 −0.029174812 1 0.598327652 0.901939163 0.218044555 1 ENSG00000075891 −0.139680455 1 0.666537779 0.859477376 0.023400093 1 ENSG00000077080 −0.291947443 1 2.05248954 0.734558921 −0.579843889 1 ENSG00000077522 −0.359543665 1 1.065057551 0.816563802 0.056205006 1 ENSG00000078295 −0.153032167 1 0.090300816 0.991823026 −0.190263243 1 ENSG00000078549 −0.548781569 1 0.436615106 0.919671237 0.282001957 1 ENSG00000078898 −0.186330302 1 0.607904762 0.874416638 0.447656564 1 ENSG00000079112 −0.174510118 1 1.290358643 0.794377353 −0.241687928 1 ENSG00000079841 −0.220370451 1 0.260822706 0.957654277 0.360367388 1 ENSG00000081248 −0.185575362 1 −0.292283267 0.939971429 0.087334946 1 ENSG00000081800 −0.315731989 1 0.415494856 0.928156195 −0.122942855 1 ENSG00000082175 −0.172803447 1 1.977891718 0.699433544 −0.170595574 1 ENSG00000084636 −0.166089061 1 0.586078349 0.853985444 −0.026623098 1 ENSG00000088340 −0.078004571 1 0.349186341 0.910714926 −0.239607349 1 ENSG00000089116 0.065319066 1 0.185915909 0.972840456 0.479688913 1 ENSG00000089199 −0.320202315 1 0.377523248 0.925166462 −0.124040006 1 ENSG00000089225 −0.186556677 1 0.596701642 0.898551048 0.187810501 1 ENSG00000091128 0.074990997 1 1.134840911 0.766090106 0.591653405 1 ENSG00000091137 −0.379948372 1 0.990697508 0.776841279 0.184013228 1 ENSG00000091656 0.068997085 1 0.573719306 0.878466837 −0.078950263 1 ENSG00000095587 −0.263611606 1 1.33832395 0.748037903 0.061668368 1 ENSG00000095637 −0.086812706 1 0.072112715 0.980464761 0.233872426 1 ENSG00000099625 0.924708632 1 4.510600591 0.630714789 −0.556807911 1 ENSG00000100033 0.392602047 1 0.416466908 0.927256113 0.024209613 1 ENSG00000100065 −0.094316814 1 1.184451382 0.737781088 0.010459367 1 ENSG00000100078 0.366462178 1 −0.809130599 0.880905808 0.273159772 1 ENSG00000100312 −0.436425953 1 −0.816265078 0.843731985 0.905100759 1 ENSG00000101004 −0.139339033 1 0.111085893 0.958051922 0.007374673 1 ENSG00000101057 0.065592927 1 −0.316760009 0.853985444 −0.363993202 1 ENSG00000101203 0.172380322 1 1.370012438 0.716500857 0.256210081 1 ENSG00000101276 0.082884294 1 1.909327866 0.760815797 −0.182694116 1 ENSG00000101680 −0.203871279 1 0.400062263 0.922861341 0.571294866 1 ENSG00000101871 0.209637567 1 −0.268771891 0.95125433 −0.036170874 1 ENSG00000102287 −0.178338056 1 0.533972134 0.907527268 0.37680991 1 ENSG00000102290 −0.633443604 1 0.867626644 0.84830486 0.353161708 1 ENSG00000102452 −0.228025142 1 0.395224547 0.921775245 0.236838494 1 ENSG00000103647 0.479287415 1 0.151419617 0.954367943 0.394859842 1 ENSG00000103855 −0.043746659 1 2.891620875 0.655801493 0.339884759 1 ENSG00000104055 0.346818998 1 2.65751116 0.661458936 0.486591696 1 ENSG00000104313 −0.089328093 1 0.904381457 0.824640952 −0.145400561 1 ENSG00000104435 −0.070221779 1 2.138741005 0.743863355 0.679714458 1 ENSG00000104537 −0.197734314 1 0.962189734 0.845260843 0.15906724 1 ENSG00000104967 −0.408162724 1 −0.241866658 0.967431863 −0.288237016 1 ENSG00000105290 0.239914511 1 0.61629374 0.884845783 −0.023517235 1 ENSG00000105357 −0.105194384 1 −0.286257636 0.937722117 0.12225136 1 ENSG00000105392 −0.140180995 1 1.350403461 0.782613897 0.12132333 1 ENSG00000105549 −0.675865699 1 0.43424405 0.933776275 −0.01546944 1 ENSG00000105605 −0.044046243 1 −0.078930301 0.997233628 −0.364251039 1 ENSG00000105664 0.234783584 1 0.117592469 0.973212079 −0.199203599 1 ENSG00000106078 −0.596349691 1 1.300744474 0.751130915 0.097709932 1 ENSG00000106304 −0.454358675 1 1.278780312 0.800133595 0.772079094 1 ENSG00000106648 −0.116446058 1 1.570956079 0.742949496 0.243774247 1 ENSG00000106689 0.428190081 1 −0.075171984 0.995803452 0.046815551 1 ENSG00000107295 −0.724258486 1 2.464703425 0.68994144 −0.086266666 1 ENSG00000107807 0.137827715 1 0.544587691 0.91119798 0.231211497 1 ENSG00000108018 −0.547468752 1 0.85269341 0.843439811 0.729297049 1 ENSG00000109101 0.538410893 1 −0.082464276 0.99353942 −0.472244905 1 ENSG00000110786 0.191502598 1 0.06896957 0.997155152 −0.238985372 1 ENSG00000110887 0.131111108 1 −0.141498179 0.979953114 0.597447393 1 ENSG00000110975 −0.281499943 1 −0.31391037 0.948383384 −0.965079899 1 ENSG00000111262 −0.466826427 1 1.142878791 0.806478894 0.642772917 1 ENSG00000111799 −0.141911997 1 0.782138184 0.832139161 0.238185895 1 ENSG00000112186 −0.024260504 1 0.733866999 0.867584145 0.324860966 1 ENSG00000112238 0.393170104 1 0.320987557 0.953891446 1.15377245 1 ENSG00000112337 −0.333294833 1 0.738233667 0.881825991 0.684826788 1 ENSG00000112499 −0.305955711 1 0.000100383 1 0.402578655 1 ENSG00000114019 0.119358618 1 0.925741653 0.7871604 −0.086135098 1 ENSG00000115041 −9.28E−06 1 −0.126754251 0.980723343 0.215502642 1 ENSG00000115155 0.197843374 1 −0.204193956 0.934184441 −0.265365542 1 ENSG00000115648 −0.639406576 1 −0.152231941 0.978305518 0.334001525 1 ENSG00000116176 0.76791399 1 −1.73419835 0.661329741 0.133366927 1 ENSG00000116721 −0.261960328 1 2.477257959 0.726218814 0.947323758 1 ENSG00000116748 −0.261856016 1 −0.621451573 0.885080104 0.613256343 1 ENSG00000116833 −0.312124377 1 −0.114723584 0.991823026 −0.210982797 1 ENSG00000117114 0.580532431 1 1.383108381 0.725470307 0.382752752 1 ENSG00000117501 −0.242525931 1 −0.356771873 0.923537499 −0.094478934 1 ENSG00000118194 −0.194780553 1 −0.045045649 1 −0.028707775 1 ENSG00000118733 −0.168306891 1 0.457037361 0.92621162 0.311727154 1 ENSG00000119125 −0.247436947 1 0.000296093 1 0.467310042 1 ENSG00000119283 −0.304232098 1 0.867258927 0.818798586 0.26292956 1 ENSG00000119547 −0.24456357 1 1.784782986 0.723496808 0.103628364 1 ENSG00000120251 −0.09039807 1 1.488077153 0.724767358 0.041642117 1 ENSG00000120332 −0.518957551 1 0.742851998 0.858968348 0.159739349 1 ENSG00000120738 −0.092535102 1 −1.368358877 0.627668963 0.333462255 1 ENSG00000121207 −0.195301435 1 0.231719596 0.969503557 0.01066207 1 ENSG00000122121 −0.109623373 1 0.864693822 0.777250738 −0.249093554 1 ENSG00000122778 −0.127759628 1 0.206228029 0.951773266 0.218362019 1 ENSG00000123243 −0.505623699 1 1.247415012 0.73235655 0.195676108 1 ENSG00000123572 −0.203352014 1 0.683557554 0.88616233 0.605013071 1 ENSG00000123977 0.488719569 1 1.503592086 0.787987908 −0.29219265 1 ENSG00000124092 0.002752214 1 0.80865262 0.840530754 −0.019073803 1 ENSG00000124253 0.27913906 1 0.276714095 0.961671576 0.284767529 1 ENSG00000124440 −0.273269415 1 1.369567585 0.762363148 0.14892327 1 ENSG00000124466 0.289895975 1 0.763945067 0.841337914 −0.097673747 1 ENSG00000124749 −0.514235619 1 1.41316074 0.762693024 0.092662892 1 ENSG00000125255 −0.027822112 1 0.044489879 1 0.555402909 1 ENSG00000125492 0.879841413 1 0.899120028 0.855882707 −0.754557485 1 ENSG00000125740 −0.208014548 1 −0.722999194 0.725297356 −0.122863284 1 ENSG00000127129 0.552586146 1 0.492127351 0.930180704 −0.351566411 1 ENSG00000128573 −0.163662169 1 1.204504792 0.787794769 −0.19108042 1 ENSG00000128917 −0.165547246 1 −0.27626558 0.951033674 0.211965616 1 ENSG00000129946 0.430826667 1 0.986068391 0.754933936 0.443270016 1 ENSG00000129990 −0.01528682 1 1.631732813 0.745077552 −0.061149728 1 ENSG00000130045 0.144594627 1 −0.278497988 0.946665677 0.334270957 1 ENSG00000130226 −0.491132363 1 0.400122019 0.917154157 0.04935684 1 ENSG00000130287 0.316905174 1 0.420188275 0.920717063 −0.642008684 1 ENSG00000130477 −0.041809609 1 0.394154009 0.905148092 −0.28674943 1 ENSG00000130508 −0.472985684 1 0.226774267 0.954203705 −0.131172062 1 ENSG00000130528 0.225433939 1 1.996649839 0.722740931 −0.363636866 1 ENSG00000130540 0.111638129 1 2.178253808 0.722217784 0.071276285 1 ENSG00000130635 −0.011150205 1 −0.056854342 0.990946263 0.076799389 1 ENSG00000131044 −0.193372839 1 0.74800611 0.828000591 0.086100403 1 ENSG00000131183 0.132968094 1 −0.764903911 0.832983886 0.131728528 1 ENSG00000131386 −0.02465071 1 −0.275997847 0.960788648 0.115571653 1 ENSG00000132297 −0.45057748 1 0.335685986 0.946406426 0.544916255 1 ENSG00000132321 −0.329452064 1 0.488440298 0.910756217 0.375351855 1 ENSG00000132639 −0.408565796 1 1.905967427 0.726386579 0.425545535 1 ENSG00000132972 −0.231290586 1 0.046000411 1 0.196976455 1 ENSG00000132975 −0.229059585 1 0.860729873 0.878558735 0.035899532 1 ENSG00000133083 −0.20329481 1 0.453081712 0.908551976 0.023848382 1 ENSG00000133110 −0.34938544 1 −0.086735544 0.992429838 −0.345362803 1 ENSG00000133124 −0.72052378 1 5.343239343 0.627668963 0.002275328 1 ENSG00000133454 −0.273389213 1 0.397760747 0.892320091 0.190816003 1 ENSG00000134240 0.097873964 1 −0.238140625 0.963217892 0.024389112 1 ENSG00000134871 0.140639269 1 −0.412550673 0.850938998 −0.091086456 1 ENSG00000135097 −0.20336144 1 0.497311089 0.937722117 −0.05653922 1 ENSG00000135409 0.204280771 1 −0.275581101 0.956707132 −0.438149966 1 ENSG00000135454 0.299571806 1 0.64554358 0.867558968 −0.208851705 1 ENSG00000135472 0.202004682 1 0.818056333 0.844324446 −0.2451995 1 ENSG00000135917 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0.606226987 0.80060544 −0.394400901 1 ENSG00000248975 −0.696722695 1 0.734788549 0.906091083 0.544431614 1 ENSG00000249119 −0.628092072 1 2.695430903 0.654655709 0.516230804 1 ENSG00000249215 0.154736731 1 −1.104123217 0.627668963 0.421347089 1 ENSG00000249267 −0.256125279 1 6.337647595 0.627668963 −0.491599301 1 ENSG00000249341 −0.880234432 1 0.98818147 0.865396845 −0.229479865 1 ENSG00000249464 −0.514600069 1 1.191697515 0.800133595 0.297158453 1 ENSG00000249584 −0.582748024 1 0.905397905 0.853001139 0.662950073 1 ENSG00000249618 −0.722916516 1 5.290100405 0.627668963 0.977525841 1 ENSG00000250049 0.565567149 1 4.638749643 0.649773207 −0.025657469 1 ENSG00000250230 −0.704990533 1 4.538960207 0.631753875 0.181526143 1 ENSG00000250420 0.006459177 1 1.165649249 0.805758306 0.299943939 1 ENSG00000250423 −0.592659414 1 0.396772621 0.930402935 0.459665173 1 ENSG00000250493 −0.290397732 1 1.178346789 0.813585817 0.221318875 1 ENSG00000250519 −0.521459048 1 0.714452444 0.886928104 0.294331525 1 ENSG00000250546 −0.546662826 1 0.645898296 0.908465718 0.158608765 1 ENSG00000251557 0.173767605 1 4.903073168 0.636992081 0.380350496 1 ENSG00000251596 −0.876823306 1 5.588638432 0.627668963 −0.068327841 1 ENSG00000251705 −0.480692883 1 0.605480991 0.905148092 0.973651682 1 ENSG00000253230 0.655376032 1 5.30777447 0.627668963 0.495127664 1 ENSG00000253288 −0.798184147 1 1.761778886 0.760843839 −0.45060209 1 ENSG00000253301 −0.266149016 1 1.768597236 0.746197395 0.101795721 1 ENSG00000253864 −0.32564569 1 1.06881022 0.853001139 −0.140130064 1 ENSG00000253871 −1.212840073 1 4.899864919 0.634030703 −0.128417963 1 ENSG00000253974 −0.494068938 1 0.695380138 0.905537291 0.183664543 1 ENSG00000254042 −0.386727632 1 1.459720136 0.770874694 0.278099271 1 ENSG00000254101 0.591458364 1 1.424625 0.813717114 0.605533171 1 ENSG00000254561 −1.139245326 1 1.50940068 0.754933936 0.059323753 1 ENSG00000256343 −0.537196458 1 1.275713507 0.828463409 0.618599755 1 ENSG00000256612 −0.117590576 1 0.231156174 0.944880397 −0.02046101 1 ENSG00000256616 0.345935051 1 5.003784965 0.641365872 −0.366243561 1 ENSG00000257008 0.848934248 1 −0.102277109 0.991463567 −0.769158893 1 ENSG00000257175 −0.023022917 1 0.488729454 0.870273599 −0.049325545 1 ENSG00000257576 −0.498873297 1 2.343052713 0.646773142 −0.636576554 1 ENSG00000257907 −0.512436099 1 0.588642968 0.88207703 −0.175387446 1 ENSG00000258628 −0.072301517 1 2.136749014 0.669487849 −0.047239297 1 ENSG00000258679 −0.525392969 1 0.183725694 0.979491691 −0.287680838 1 ENSG00000259010 −0.240255224 1 0.197786861 0.956817068 0.060147849 1 ENSG00000259156 −0.563040176 1 0.6762214 0.863255934 0.753375248 1 ENSG00000259176 −0.530044663 1 2.106754077 0.722808749 1.540061541 1 ENSG00000259380 −0.58933832 1 5.11915559 0.627668963 0.287497927 1 ENSG00000259458 0.414725309 1 0.442861703 0.946558275 0.559307634 1 ENSG00000259790 −0.210937874 1 −1.346601099 0.655801493 0.633164315 1 ENSG00000259841 −0.79107658 1 1.107914278 0.836986961 0.715989445 1 ENSG00000260027 0.660153746 1 0.476035227 0.906333972 −0.099631653 1 ENSG00000260072 −0.789539115 1 0.863110797 0.821508914 0.12828000 1 ENSG00000260290 0.104471538 1 −0.836870858 0.675458806 0.197375256 1 ENSG00000260305 −1.028600501 1 4.744023963 0.628886787 0.698875009 1 ENSG00000260411 −0.128473671 1 0.041607103 1 −0.112690723 1 ENSG00000260759 −0.192880296 1 0.94955643 0.867746032 −0.051041077 1 ENSG00000261104 −1.123431613 1 4.860266739 0.657456325 0.120349508 1 ENSG00000261115 −0.234381639 1 1.512747564 0.661458936 0.462069476 1 ENSG00000261177 −0.061233144 1 1.137537332 0.817387218 −0.510065734 1 ENSG00000261275 −0.4281369 1 0.786323262 0.890831721 0.732924735 1 ENSG00000261466 −0.090787283 1 4.851984871 0.638396538 −0.094510196 1 ENSG00000261623 −0.095785762 1 1.080068661 0.844324446 0.864325115 1 ENSG00000261649 −0.660535388 1 2.043392484 0.73954672 −0.330000743 1 ENSG00000261949 −0.475251506 1 −0.763663195 0.850814909 0.089947054 1 ENSG00000262691 0.252943534 1 5.081334361 0.627668963 −0.401503894 1 ENSG00000263711 0.040985491 1 5.347698255 0.639135327 0.507100706 1 ENSG00000264954 0.634210849 1 −1.528455556 0.684013324 −0.345406349 1 ENSG00000265041 0.15210652 1 0.273182081 0.961671576 0.078015834 1 ENSG00000266172 −0.456128633 1 2.845807132 0.667458257 0.135393857 1 ENSG00000266795 0.388194442 1 2.036976544 0.746202308 −0.11233752 1 ENSG00000267324 −0.179694156 1 −0.10327279 0.993188995 0.459785761 1 ENSG00000268388 −0.295612418 1 1.970132857 0.724282844 0.544203429 1 ENSG00000268460 −0.008495927 1 0.828130352 0.869925678 0.024780764 1 ENSG00000269332 0.138816664 1 1.031492879 0.835394728 0.410194088 1

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Example 2 AC2 and AC3 Genes and PRIME Cell Markers

RNAs and Markers

As detailed above, RNA analysis of fingerstick blood samples from RA patients has identified RNAs suitable as markers of RA flares. A first set of markers and RNAs, denoted AC2, is increased 2 weeks prior to flare. AC2 RNAs are enriched with developmental pathways for naive B cells and leukocytes. A second set of markers, denoted AC3, is increased the week prior to flare and is then decreased for the duration of the flare. AC3 is enriched for pathways not typical of blood samples, particularly cartilage morphogenesis, endochondral bone growth, extracellular matrix organization. AC3 is enriched with sublining fibroblast genes (CD34+HLADR+DKK3+)._The AC2 markers are listed below in Table 7. AC3 gene markers are listed below in Table 8.

TABLE 7 AC2 GENES Ensembl Symbol Description Score/AUC ENSG00000204632 HLA-G “major histocompatibility complex, class 1, G 5.77E−05 [Source:HGNC Symbol;Acc:HGNC:4964]” ENSG00000184792 OSBP2 oxysterol binding protein 2 6.39E−05 [Source:HGNC Symbol;Acc:HGNC:8504] ENSG00000198892 SHISA4 shisa family member 4 0.00012762 [Source:HGNC Symbol;Acc:HGNC:27139] ENSG00000187017 ESPN espin 0.000131036 [Source:HGNC Symbol;Acc:HGNC:13281] ENSG00000233762 0.000323289 ENSG00000175130 MARCKSL1 MARCKS like 1 0.000358619 [Source:HGNC Symbol;Acc:HGNC:7142] ENSG00000125534 PPDPF pancreatic progenitor cell differentiation and proliferation factor 0.00037025 [Source:HGNC Symbol;Acc:HGNC:16142] ENSG00000158856 DMTN dematin actin binding protein 0.000376535 [Source:HGNC Symbol;Acc:HGNC:3382] ENSG00000121413 ZSCAN18 zinc finger and SCAN domain containing 18 0.000443873 [Source:HGNC Symbol;Acc:HGNC:21037] ENSG00000230715 0.000528797 ENSG00000215030 RPL13P12 ribosomal protein L13 pseudogene 12 0.000588454 [Source:HGNC Symbol;Acc:HGNC:35701] ENSG00000146540 C7orf50 chromosome 7 open reading frame 50 0.000639272 [Source:HGNC Symbol;Acc:HGNC:22421] ENSG00000029534 ANK1 ankyrin 1 0.000697583 [Source:HGNC Symbol;Acc:HGNC:492] ENSG00000121104 FAM117A family with sequence similarity 117 member A 0.000697583 [Source:HGNC Symbol;Acc:HGNC:24179] ENSG00000260231 JHDM1D-AS1 JHDM1D antisense RNA 1 (head to head) 0.00070319 [Source:HGNC Symbol;Acc:HGNC:48959] ENSG00000211895 IGHA1 immunoglobulin heavy constant alpha l 0.000707226 [Source:HGNC Symbol;Acc:HGNC:5478] ENSG00000173581 CCDC106 coiled-coil domain containing 106 0.000730947 [Source:HGNC Symbol;Acc:HGNC:30181] ENSG00000008441 NFIX nuclear factor I X 0.000837162 [Source:HGNC Symbol;Acc:HGNC:7788] ENSG00000105701 FKBP8 FK506 binding protein 8 0.000994972 [Source:HGNC Symbol;Acc:HGNC:3724] ENSG00000079308 TNS1 tensin 1 0.00113151 [Source:HGNC Symbol;Acc:HGNC:11973] ENSG00000264063 MIR3687-2 microRNA 3687-2 0.001218296 [Source:HGNC Symbol;Acc:HGNC:50835] ENSG00000049089 COL9A2 collagen type IX alpha 2 chain 0.001236713 [Source:HGNC Symbol;Acc:HGNC:2218] ENSG00000126461 SCAF1 SR-related CTD associated factor 1 0.00126185 [Source:HGNC Symbol;Acc:HGNC:30403] ENSG00000243679 0.001292673 ENSG00000169136 ATF5 activating transcription factor 5 0.001421682 [Source:HGNC Symbol;Acc:HGNC:790] ENSG00000181588 MEX3D mex-3 RNA binding family member D 0.001421682 [Source:HGNC Symbol;Acc:HGNC:16734] ENSG00000103257 SLC7A5 solute carrier family 7 member 5 0.001574737 [Source:HGNC Symbol;Acc:HGNC:11063] ENSG00000175931 UBE2O ubiquitin conjugating enzyme E2 O 0.001669619 [Source:HGNC Symbol;Acc:HGNC:29554] ENSG00000065268 WDR18 WD repeat domain 18 0.001764407 [Source:HGNC Symbol;Acc:HGNC:17956] ENSG00000130300 PLVAP plasmalemma vesicle associated protein 0.001779673 [Source:HGNC Symbol;Acc:HGNC:13635] ENSG00000232434 AJM1 apical junction component 1 homolog 0.001937905 [Source:HGNC Symbol;Acc:HGNC:37284] ENSG00000197256 KANK2 KN motif and ankyrin repeat domains 2 0.001945859 [Source:HGNC Symbol;Acc:HGNC:29300] ENSG00000229809 ZNF688 zinc finger protein 688 0.002041059 [Source:HGNC Symbol;Acc:HGNC:30489] ENSG00000130433 CACNG6 calcium voltage-gated channel auxiliary subunit gamma 6 0.002327494 [Source:HGNC Symbol;Acc:HGNC:13625] ENSG00000126254 RBM42 RNA binding motif protein 42 0.002342133 [Source:HGNC Symbol;Acc:HGNC:28117] ENSG00000013306 SLC25A39 solute carrier family 25 member 39 0.002354141 [Source:HGNC Symbol;Acc:HGNC:24279] ENSG00000179837 NA NA 0.002482976 ENSG00000265714 NA NA 0.002482976 ENSG00000172460 PRSS30P “serine protease 30, pseudogene 0.002490713 [Source:HGNC Symbol;Acc:HGNC:28753]” ENSG00000104983 CCDC61 coiled-coil domain containing 61 0.002565172 [Source:HGNC Symbol;Acc:HGNC:33629] ENSG00000211898 IGHD immunoglobulin heavy constant delta 0.002565172 [Source:HGNC Symbol;Acc:HGNC:5480] ENSG00000055118 KCNH2 potassium voltage-gated channel subfamily H member 2 0.002637584 [Source:HGNC Symbol;Acc:HGNC:6251] ENSG00000260335 0.002639596 ENSG00000104903 LYL1 “LYL1, basic helix-loop-helix family member 0.002696079 [Source:HGNC Symbol;Acc:HGNC:6734]” ENSG00000099958 DERL3 derlin 3 0.002709927 [Source:HGNC Symbol;Acc:HGNC:14236] ENSG00000179526 SHARPIN SHANK associated RH domain interactor 0.002709927 [Source:HGNC Symbol;Acc:HGNC:25321] ENSG00000133069 TMCC2 transmembrane and coiled-coil domain family 2 0.002940811 [Source:HGNC Symbol;Acc:HGNC:24239] ENSG00000240342 RPS2P5 ribosomal protein S2 pseudogene 5 0.002940811 [Source:HGNC Symbol;Acc:HGNC:31386] ENSG00000264462 MIR3648-2 microRNA 3648-2 0.003313878 [Source:HGNC Symbol;Acc:HGNC:50843] ENSG00000256576 LINC02361 long intergenic non-protein coding RNA 2361 0.003383286 [Source:HGNC Symbol;Acc:HGNC:53283] ENSG00000007968 E2F2 E2F transcription factor 2 [ 0.003400809 [Source:HGNC Symbol;Acc:HGNC:3114] ENSG00000141858 SAMD1 sterile alpha motif domain containing 1 0.003623721 [Source:HGNC Symbol;Acc:HGNC:17958] ENSG00000126705 AHDC1 AT-hook DNA binding motif containing 1 0.004035577 [Source:HGNC Symbol;Acc:HGNC:25230] ENSG00000141456 PELP1 “proline, glutamate and leucine rich protein 1 0.00422876 [Source:HGNC Symbol;Acc:HGNC:30134]” ENSG00000159713 TPPP3 tubulin polymerization promoting protein family member 3 0.004525344 [Source:HGNC Symbol;Acc:HGNC:24162] ENSG00000104897 SF3A2 splicing factor 3a subunit 2 0.004539725 [Source:HGNC Symbol;Acc:HGNC:10766] ENSG00000063245 EPN1 epsin 1 0.004540184 [Source:HGNC Symbol;Acc:HGNC:21604] ENSG00000162783 IER5 immediate early response 5 0.004549021 [Source:HGNC Symbol;Acc:HGNC:5393] ENSG00000141582 CBX4 chromobox 4 0.004686524 [Source:HGNC Symbol;Acc:HGNC:1554] ENSG00000168159 RNF187 ring finger protein 187 0.004686524 [Source:HGNC Symbol;Acc:HGNC:27146] ENSG00000136826 KLF4 Kruppel like factor 4 0.004891089 [Source:HGNC Symbol;Acc:HGNC:6348] ENSG00000237214 0.004891089 ENSG00000066336 SPI1 Spi-1 proto-oncogene 0.005082358 [Source:HGNC Symbol;Acc:HGNC:11241] ENSG00000172270 BSG basigin (Ok blood group) 0.005082358 [Source:HGNC Symbol;Acc:HGNC:1116] ENSG00000173868 PHOSPHO1 phosphoethanolamine/phosphocholine phosphatase 0.005082358 [Source:HGNC Symbol;Acc:HGNC:16815] ENSG00000167182 SP2 Sp2 transcription factor 0.005118791 [Source:HGNC Symbol;Acc:HGNC:11207] ENSG00000104805 NUCB1 nucleobindin 1 0.005119064 [Source:HGNC Symbol;Acc:HGNC:8043] ENSG00000099381 SETD1A SET domain containing 1A 0.00514547 [Source:HGNC Symbol;Acc:HGNC:29010] ENSG00000185340 GAS2L1 growth arrest specific 2 like 1 0.00514547 [Source:HGNC Symbol;Acc:HGNC:16955] ENSG00000007541 PIGQ phosphatidylinositol glycan anchor biosynthesis class Q 0.005166641 [Source:HGNC Symbol;Acc:HGNC:14135] ENSG00000105610 KLF1 Kruppel like factor 1 0.005217627 [Source:HGNC Symbol;Acc:HGNC:6345] ENSG00000137193 PIMI “Pim-1 proto-oncogene, serine/threonine kinase 0.005247531 [Source:HGNC Symbol;Acc:HGNC:8986]” ENSG00000171552 BCL2L1 BCL2 like 1 0.005530506 [Source:HGNC Symbol;Acc:HGNC:992] ENSG00000172889 EGFL7 EGF like domain multiple 7 0.005530506 [Source:HGNC Symbol;Acc:HGNC:20594] ENSG00000213402 PTPRCAP “protein tyrosine phosphatase, receptor type C associated protein 0.00560032 [Source:HGNC Symbol;Acc:HGNC:9667]” ENSG00000099330 OCEL1 occludin/ELL domain containing 1 0.005671418 [Source:HGNC Symbol;Acc:HGNC:26221] ENSG00000147443 DOK2 docking protein 2 0.005857886 [Source:HGNC Symbol;Acc:HGNC:2991] ENSG00000182240 BACE2 beta-site APP-cleaving enzyme 2 0.005857886 [Source:HGNC Symbol;Acc:HGNC:934] ENSG00000170128 GPR25 G protein-coupled receptor 25 0.006101348 [Source:HIGNC Symbol; Acc:HGNC:4480] ENSG00000140406 TLNRD1 talin rod domain containing 1 0.0061541 [Source:HGNC Symbol;Acc:HGNC:13519] ENSG00000117394 SLC2A1 solute carrier family 2 member 1 0.006158727 [Source:HGNC Symbol;Acc:HGNC:11005] ENSG00000141854 MISP3 MISP family member 3 0.006204755 [Source:HGNC Symbol;Acc:HGNC:26963] ENSG00000129757 CDKN1C cyclin dependent kinase inhibitor 1C 0.006380434 [Source:HGNC Symbol;Acc:HGNC:1786] ENSG00000186891 TNFRSF18 TNF receptor superfamily member 18 0.006421961 [Source:HGNC Symbol;Acc:HGNC:11914] ENSG00000184897 H1FX H1 histone family member X 0.006465512 [Source:HGNC Symbol;Acc:HGNC:4722] ENSG00000185236 RAB11B “RAB11B, member RAS oncogene family 0.006602734 [Source:HGNC Symbol;Acc:HGNC:9761]” ENSG00000030582 GRN granulin precursor 0.006751675 [Source:HGNC Symbol;Acc:HGNC:4601] ENSG00000071564 TCF3 transcription factor 3 0.006772165 [Source:HGNC Symbol;Acc:HGNC:11633] ENSG00000267749 0.006848491 ENSG00000105373 NOP53 NOP53 ribosome biogenesis factor 0.006952696 [Source:HGNC Symbol;Acc:HGNC:4333] ENSG00000240445 FOXO3B forkhead box O3B pseudogene 0.006952696 [Source:HGNC Symbol;Acc:HGNC:3822] ENSG00000127528 KLF2 Kruppel like factor 2 0.00698206 [Source:HGNC Symbol;Acc:HGNC:6347] ENSG00000254858 MPV17L2 MPV17 mitochondrial inner membrane protein like 2 0.006997113 [Source:HGNC Symbol;Acc:HGNC:28177] ENSG00000130595 TNNT3 “troponin T3, fast skeletal type 0.007133196 [Source:HGNC Symbol;Acc:HGNC:11950]” ENSG00000130749 ZC3H4 zinc finger CCCH-type containing 4 0.007141116 [Source:HGNC Symbol;Acc:HGNC:17808] ENSG00000132819 RBM38 RNA binding motif protein 38 0.007141116 [Source:HGNC Symbol;Acc:HGNC:15818] ENSG00000135925 WNT10A Wnt family member 10A 0.007141116 [Source:HGNC Symbol;Acc:HGNC:13829] ENSG00000205639 MFSD2B major facilitator superfamily domain containing 2B 0.007141116 [Source:HGNC Symbol;Acc:HGNC:37207] ENSG00000213763 ACTBP2 “actin, beta pseudogene 2 0.007141116 [Source:HGNC Symbol;Acc:HGNC:135]” ENSG00000261221 ZNF865 zinc finger protein 865 0.007141116 [Source:HGNC Symbol;Acc:HGNC:38705] ENSG00000171611 PTCRA pre T cell antigen receptor alpha 0.007255358 [Source:HGNC Symbol;Acc:HGNC:21290] ENSG00000161642 ZNF385A zinc finger protein 385A 0.007304748 [Source:HGNC Symbol;Acc:HGNC:17521] ENSG00000226608 FTLP3 ferritin light chain pseudogene 3 0.007304748 [Source:HGNC Symbol;Acc:HGNC:4000] ENSG00000170684 ZNF296 zinc finger protein 296 0.007327997 [Source:HGNC Symbol;Acc:HGNC:15981] ENSG00000213638 ADAT3 “adenosine deaminase, tRNA specific 3 0.007343983 [Source:HGNC Symbol;Acc:HGNC:25151]” ENSG00000179262 RAD23A “RAD23 homolog A, nucleotide excision repair protein 0.0073448 [Source:HGNC Symbol;Acc:HGNC:9812]” ENSG00000196126 HLA-DRB1 “major histocompatibility complex, class II, DR beta l 0.00745996 [Source:HGNC Symbol;Acc:HGNC:4948]” ENSG00000197149 0.007535198 ENSG00000213820 RPL13P2 ribosomal protein L13 pseudogene 2 0.007619923 [Source:HGNC Symbol;Acc:HGNC:16342] ENSG00000225331 LINC01678 long intergenic non-protein coding RNA 1678 0.007619923 [Source:HGNC Symbol;Acc:HGNC:52466] ENSG00000235605 0.007619923 ENSG00000183092 BEGAIN brain enriched guanylate kinase associated 0.007755013 [Source:HGNC Symbol;Acc:HGNC:24163] ENSG00000105369 CD79A CD79a molecule 0.007835589 [Source:HGNC Symbol;Acc:HGNC:1698] ENSG00000160256 FAM207A family with sequence similarity 207 member A 0.007901726 [Source:HGNC Symbol;Acc:HGNC:15811] ENSG00000105516 DBP D-box binding PAR bZIP transcription factor 0.00795596 [Source:HGNC Symbol;Acc:HGNC:2697] ENSG00000179094 PER1 period circadian regulator 1 0.008010463 [Source:HGNC Symbol;Acc:HGNC:8845] ENSG00000154146 NRGN neurogranin 0.008019602 [Source:HGNC Symbol;Acc:HGNC:8000] ENSG00000160813 PPP1R35 protein phosphatase 1 regulatory subunit 35 0.008019602 [Source:HGNC Symbol;Acc:HGNC:28320] ENSG00000152082 MZT2B mitotic spindle organizing protein 2B 0.008149414 [Source:HGNC Symbol;Acc:HGNC:25886] ENSG00000115274 INO80B INO80 complex subunit B 0.008388785 [Source:HGNC Symbol;Acc:HGNC:13324] ENSG00000185112 FAM43A family with sequence similarity 43 member A 0.008409751 [Source:HGNC Symbol;Acc:HGNC:26888] ENSG00000130592 LSP1 lymphocyte-specific protein 1 0.00866593 [Source:HGNC Symbol;Acc:HGNC:6707] ENSG00000077348 EXOSC5 exosome component 5 0.008679008 [Source:HGNC Symbol;Acc:HGNC:24662] ENSG00000196498 NCOR2 nuclear receptor corepressor 2 0.008729326 [Source:HGNC Symbol;Acc:HGNC:7673] ENSG00000132382 MYBBP1A MYB binding protein la 0.008886691 [Source:HGNC Symbol;Acc:HGNC:7546] ENSG00000104885 DOT1L DOT1 like histone lysine methyltransferase 0.008912378 [Source:HGNC Symbol;Acc:HGNC:24948] ENSG00000153443 UBALD1 UBA like domain containing 1 0.008912378 [Source:HGNC Symbol;Acc:HGNC:29576] ENSG00000070182 SPTB “spectrin beta, erythrocytic 0.008927471 [Source:HGNC Symbol;Acc:HGNC:11274]” ENSG00000168517 HEXIM2 hexamethylene bisacetamide inducible 2 0.008959412 [Source:HGNC Symbol;Acc:HGNC:28591] ENSG00000090674 MCOLN1 mucolipin 1 0.009327518 [Source:HGNC Symbol;Acc:HGNC:13356] ENSG00000198816 ZNF358 zinc finger protein 358 0.009506451 [Source:HGNC Symbol;Acc:HGNC:16838] ENSG00000175334 BANF1 barrier to autointegration factor 1 0.009647997 [Source:HGNC Symbol;Acc:HGNC:17397] ENSG00000125520 SLC2A4RG SLC2A4 regulator 0.009686596 [Source:HGNC Symbol;Acc:HGNC:15930] ENSG00000141084 RANBP10 RAN binding protein 10 0.009715508 [Source:HGNC Symbol;Acc:HGNC:29285] ENSG00000149016 TUT1 “terminal uridylyl transferase 1, U6 snRNA-specific 0.009768686 [Source:HGNC Symbol;Acc:HGNC:26184]” ENSG00000178951 ZBTB7A zinc finger and BTB domain containing 7A 0.009810065 [Source:HGNC Symbol;Acc:HGNC:18078] ENSG00000186111 PIP5K1C phosphatidylinositol-4-phosphate 5-kinase type 1 gamma 0.009810065 [Source:HGNC Symbol;Acc:HGNC:8996] ENSG00000184481 FOXO4 forkhead box O4 0.009820284 [Source:HGNC Symbol;Acc:HGNC:7139] ENSG00000064961 HMG20B high mobility group 20B 0.009858965 [Source:HGNC Symbol;Acc:HGNC:5002] ENSG00000108309 RUNDC3A RUN domain containing 3A 0.010055443 [Source:HGNC Symbol;Acc:HGNC:16984] ENSG00000130165 ELOF1 elongation factor 1 homolog 0.010212535 [Source:HGNC Symbol;Acc:HGNC:28691] ENSG00000130159 ECSIT ECSIT signalling integrator 0.010245658 [Source:HGNC Symbol;Acc:HGNC:29548] ENSG00000244560 0.010245658 ENSG00000125148 MT2A metallothionein 2A 0.01061889 [Source:HGNC Symbol;Acc:HGNC:7406] ENSG00000131116 ZNF428 zinc finger protein 428 0.010712491 [Source:HGNC Symbol;Acc:HGNC:20804] ENSG00000105617 LENG1 leukocyte receptor cluster member 1 0.010999325 [Source:HGNC Symbol;Acc:HGNC:15502] ENSG00000139718 SETD1B SET domain containing IB 0.011038344 [Source:HGNC Symbol;Acc:HGNC:29187] ENSG00000106665 CLIP2 CAP-Gly domain containing linker protein 2 0.011064297 [Source:HGNC Symbol;Acc:HGNC:2586] ENSG00000130821 SLC6A8 solute carrier family 6 member 8 0.011213055 [Source:HGNC Symbol;Acc:HGNC:11055] ENSG00000184232 OAF out at first homolog 0.011286635 [Source:HGNC Symbol;Acc:HGNC:28752] ENSG00000179820 MYADM myeloid associated differentiation marker 0.011330192 [Source:HGNC Symbol;Acc:HGNC:7544] ENSG00000127580 WDR24 WD repeat domain 24 0.011570001 [Source:HGNC Symbol;Acc:HGNC:20852] ENSG00000004939 SLC4A1 solute carrier family 4 member 1 (Diego blood group) 0.011732314 [Source:HGNC Symbol;Acc:HGNC:11027] ENSG00000130522 JUND “JunD proto-oncogene, AP-1 transcription factor subunit 0.011813745 [Source:HGNC Symbol;Acc:HGNC:6206]” ENSG00000148362 PAXX “PAXX, non-homologous end joining factor 0.011821074 [Source:HGNC Symbol;Acc:HGNC:27849]” ENSG00000262902 MTCO1P40 mitochondrially encoded cytochrome c oxidase I pseudogene 40 0.011821074 [Source:HGNC Symbol;Acc:HGNC:52105] ENSG00000167671 UBXN6 UBX domain protein 6 0.011831088 [Source:HGNC Symbol;Acc:HGNC:14928] ENSG00000125457 MIF4GD MIF4G domain containing 0.011851589 [Source:HGNC Symbol;Acc:HGNC:24030] ENSG00000146066 HIGD2A HIGI hypoxia inducible domain family member 2A 0.011914767 [Source:HGNC Symbol;Acc:HGNC:28311] ENSG00000184221 OLIG1 oligodendrocyte transcription factor 1 0.011914767 [Source:HGNC Symbol;Acc:HGNC:16983] ENSG00000260316 0.0119947 ENSG00000124762 CDKN1A cyclin dependent kinase inhibitor 1A 0.012077375 [Source:HGNC Symbol;Acc:HGNC:1784] ENSG00000103148 NPRL3 “NPR3 like, GATOR1 complex subunit 0.012137266 [Source:HGNC Symbol;Acc:HGNC:14124]” ENSG00000179115 FARSA phenylalanyl-tRNA synthetase alpha subunit 0.012137266 [Source:HGNC Symbol;Acc:HGNC:3592] ENSG00000120896 SORBS3 sorbin and SH3 domain containing 3 0.012150664 [Source:HGNC Symbol;Acc:HGNC:30907] ENSG00000174886 NDUFA11 NADH:ubiquinone oxidoreductase subunit A11 0.012268883 [Source:HGNC Symbol;Acc:HGNC:20371] ENSG00000102145 GATA1 GAT A binding protein 1 0.012285964 [Source:HGNC Symbol;Acc:HGNC:4170] ENSG00000166428 PLD4 phospholipase D family member 4 0.012401569 [Source:HGNC Symbol;Acc:HGNC:23792] ENSG00000213015 ZNF580 zinc finger protein 580 0.012630003 [Source:HGNC Symbol;Acc:HGNC:29473] ENSG00000142544 CTU1 cytosolic thiouridylase subunit 1 0.012676606 [Source:HIGNC Symbol; Acc:HGNC:29590] ENSG00000085644 ZNF213 zinc finger protein 213 0.012935817 [Source:HGNC Symbol;Acc:HGNC:13005] ENSG00000003249 DBNDD1 dysbindin domain containing 1 0.013109402 [Source:HGNC Symbol;Acc:HGNC:28455] ENSG00000221288 MIR663B microRNA 663b 0.013333238 [Source:HGNC Symbol;Acc:HGNC:35270] ENSG00000042062 RIPOR3 RIPOR family member 3 0.013356858 [Source:HGNC Symbol;Acc:HGNC:16168] ENSG00000105329 TGFB1 transforming growth factor beta 1 0.013356858 [Source:HGNC Symbol;Acc:HGNC:11766] ENSG00000116871 MAP7D1 MAP7 domain containing 1 0.013356858 [Source:HGNC Symbol;Acc:HGNC:25514] ENSG00000168298 HIST1H1E histone cluster 1 H1 family member e 0.013400191 [Source:HGNC Symbol;Acc:HGNC:4718] ENSG00000127666 TICAM1 toll like receptor adaptor molecule 1 0.013447765 [Source:HIGNC Symbol; Acc:HGNC:18348] ENSG00000166886 NAB2 NGFI-A binding protein 2 0.013572419 [Source:HGNC Symbol;Acc:HGNC:7627] ENSG00000112787 FBRSL1 fibrosin like 1 0.013760569 [Source:HGNC Symbol;Acc:HGNC:29308] ENSG00000100243 CYB5R3 cytochrome b5 reductase 3 0.013883197 [Source:HGNC Symbol;Acc:HGNC:2873] ENSG00000197457 STMN3 stathmin 3 0.013964273 [Source:HGNC Symbol;Acc:HGNC:15926] ENSG00000255441 0.013965194 ENSG00000173801 JUP junction plakoglobin 0.014437619 [Source:HGNC Symbol;Acc:HGNC:6207] ENSG00000224614 TNK2-AS1 TNK2 antisense RNA 1 0.014437619 [Source:HGNC Symbol;Acc:HGNC:49093] ENSG00000058453 CROCC “ciliary rootlet coiled-coil, rootletin 0.014522615 [Source:HGNC Symbol;Acc:HGNC:21299]” ENSG00000079313 REXO1 RNA exonuclease l homolog 0.014579462 [Source:HGNC Symbol;Acc:HGNC:24616] ENSG00000154102 C16orf74 chromosome 16 open reading frame 74 0.014732236 [Source:HGNC Symbol;Acc:HGNC:23362] ENSG00000172650 AGAP5 “ArfGAP with GTPase domain, ankyrin repeat and PH domain 5 0.014761715 [Source:HGNC Symbol;Acc:HGNC:23467]” ENSG00000159733 ZFYVE28 zinc finger FYVE-type containing 28 0.014792652 [Source:HGNC Symbol;Acc:HGNC:29334] ENSG00000019582 CD74 CD74 molecule 0.014946895 [Source:HGNC Symbol;Acc:HGNC:1697] ENSG00000211771 TRBJ2-7 T cell receptor beta joining 2-7 0.014961068 [Source:HGNC Symbol;Acc:HGNC:12175] ENSG00000214309 MBLAC1 metallo-beta-lactamase domain containing 1 0.014976932 [Source:HGNC Symbol;Acc:HGNC:22180] ENSG00000187266 EPOR erythropoietin receptor 0.015342955 [Source:HGNC Symbol;Acc:HGNC:3416] ENSG00000108106 UBE2S ubiquitin conjugating enzyme E2 S 0.015459542 [Source:HGNC Symbol;Acc:HGNC:17895] ENSG00000185838 GNB1L G protein subunit beta 1 like 0.015552452 [Source:HGNC Symbol;Acc:HGNC:4397] ENSG00000228594 FNDC10 fibronectin type III domain containing 10 0.015552452 [Source:HGNC Symbol;Acc:HGNC:42951] ENSG00000126464 PRR12 proline rich 12 0.015622838 [Source:HGNC Symbol;Acc:HGNC:29217] ENSG00000084092 NOA1 nitric oxide associated 1 0.015753463 [Source:HGNC Symbol;Acc:HGNC:28473] ENSG00000105227 PRX periaxin 0.015787169 [Source:HGNC Symbol;Acc:HGNC:13797] ENSG00000260401 0.015787169 ENSG00000159840 ZYX zyxin 0.015829354 [Source:HGNC Symbol;Acc:HGNC:13200] ENSG00000197483 ZNF628 zinc finger protein 628 0.015834462 [Source:HGNC Symbol;Acc:HGNC:28054] ENSG00000182572 NA NA 0.015908819 ENSG00000154035 NA NA 0.015942034 ENSG00000161618 ALDH16A1 aldehyde dehydrogenase 16 family member A1 0.015942034 [Source:HGNC Symbol;Acc:HGNC:28114] ENSG00000124575 HIST1H1D histone cluster 1 H1 family member d 0.015948868 [Source:HGNC Symbol;Acc:HGNC:4717] ENSG00000196092 PAX5 paired box 5 0.01597311 [Source:HGNC Symbol;Acc:HGNC:8619] ENSG00000105429 MEGF8 multiple EGF like domains 8 0.015986308 [Source:HGNC Symbol;Acc:HGNC:3233] ENSG00000213753 CENPBD1P1 CENPB DNA-binding domains containing 1 pseudogene 1 0.016008143 [Source:HGNC Symbol;Acc:HGNC:28421] ENSG00000179627 ZBTB42 zinc finger and BTB domain containing 42 0.016166469 [Source:HGNC Symbol;Acc:HGNC:32550] ENSG00000107816 LZTS2 leucine zipper tumor suppressor 2 0.016243979 [Source:HGNC Symbol;Acc:HGNC:29381] ENSG00000183779 ZNF703 zinc finger protein 703 0.016243979 [Source:HIGNC Symbol; Acc:HGNC:25883] ENSG00000203950 RTL8A retrotransposon Gag like 8A 0.01630694 [Source:HGNC Symbol;Acc:HGNC:24514] ENSG00000088826 SMOX spermine oxidase 0.016416472 [Source:HGNC Symbol;Acc:HGNC:15862] ENSG00000105298 CACTIN “cactin, spliceosome C complex subunit 0.016416472 [Source:HGNC Symbol;Acc:HGNC:29938]” ENSG00000137218 FRS3 fibroblast growth factor receptor substrate 3 0.016416472 [Source:HGNC Symbol;Acc:HGNC:16970] ENSG00000175550 DRAP1 DRI associated protein 1 0.016587059 [Source:HGNC Symbol;Acc:HGNC:3019] ENSG00000166165 CKB creatine kinase B 0.01659925 [Source:HGNC Symbol;Acc:HGNC:1991] ENSG00000162366 PDZK1IP1 PDZK1 interacting protein 1 0.016705327 [Source:HGNC Symbol;Acc:HGNC:16887] ENSG00000184428 TOP1MTDNA topoisomerase 1 mitochondrial 0.016722415 [Source:HGNC Symbol;Acc:HGNC:29787] ENSG00000130479 MAP1S microtubule associated protein 1S 0.016796937 [Source:HGNC Symbol;Acc:HGNC:15715] ENSG00000171222 SCAND1 SCAN domain containing 1 0.016821415 [Source:HGNC Symbol;Acc:HGNC:10566] ENSG00000171223 JUNB “JunB proto-oncogene, AP-1 transcription factor subunit 0.016966042 [Source:HGNC Symbol;Acc:HGNC:6205]” ENSG00000107902 LHPP phospholysine phosphohistidine inorganic pyrophosphate phosphatase 0.017052413 [Source:HGNC Symbol;Acc:HGNC:30042] ENSG00000170271 FAXDC2 fatty acid hydroxylase domain containing 2 0.017052413 [Source:HGNC Symbol;Acc:HGNC:1334] ENSG00000100325 ASCC2 activating signal cointegrator 1 complex subunit 2 0.017132234 [Source:HGNC Symbol;Acc:HGNC:24103] ENSG00000142694 EVA1B eva-1 homolog B 0.017132234 [Source:HGNC Symbol;Acc:HGNC:25558] ENSG00000064201 TSPAN32 tetraspanin 32 0.017210927 [Source:HGNC Symbol;Acc:HGNC:13410] ENSG00000157911 PEX10 peroxisomal biogenesis factor 10 0.017211726 [Source:HGNC Symbol;Acc:HGNC:8851] ENSG00000079432 CIC capicua transcriptional repressor 0.017339051 [Source:HGNC Symbol;Acc:HGNC:14214] ENSG00000188825 LINC00910 long intergenic non-protein coding RNA 910 0.017339051 [Source:HGNC Symbol;Acc:HGNC:44361] ENSG00000196961 AP2A1 adaptor related protein complex 2 alpha 1 subunit 0.017339051 [Source:HGNC Symbol;Acc:HGNC:561] ENSG00000214279 SCART1 scavenger receptor family member expressed on T cells 1 0.017339051 [Source:HGNC Symbol;Acc:HGNC:32411] ENSG00000272449 0.017339051 ENSG00000104973 MED25 mediator complex subunit 25 0.017392388 [Source:HGNC Symbol;Acc:HGNC:28845] ENSG00000180767 CHST13 carbohydrate sulfotransferase 13 0.017392388 [Source:HGNC Symbol;Acc:HGNC:21755] ENSG00000227232 WASH7P WAS protein family homolog 7 pseudogene 0.017392388 [Source:HGNC Symbol;Acc:HGNC:38034] ENSG00000162302 RPS6KA4 ribosomal protein S6 kinase A4 0.017767827 [Source:HGNC Symbol;Acc:HGNC:10433] ENSG00000136840 ST6GALNAC4 “ST6 N-acetylgalactosaminide alpha-2,6-sialyltransferase 4 0.017832974 [Source:HGNC Symbol;Acc:HGNC:17846]” ENSG00000160404 TOR2A torsin family 2 member A 0.018020454 [Source:HGNC Symbol;Acc:HGNC:11996] ENSG00000233038 0.018071818 ENSG00000243449 C4orf48 chromosome 4 open reading frame 48 0.018116836 [Source:HGNC Symbol;Acc:HGNC:34437] ENSG00000160050 CCDC28B coiled-coil domain containing 28B 0.01812987 [Source:HGNC Symbol;Acc:HGNC:28163] ENSG00000138623 SEMA7A semaphorin 7A (John Milton Hagen blood group) 0.01834001 [Source:HGNC Symbol;Acc:HGNC:10741] ENSG00000101439 CST3 cystatin C 0.018421259 [Source:HGNC Symbol;Acc:HGNC:2475] ENSG00000100368 CSF2RB colony stimulating factor 2 receptor beta common subunit 0.01865112 [Source:HGNC Symbol;Acc:HGNC:2436] ENSG00000006015 REX1BD required for excision 1-B domain containing 0.01871477 [Source:HGNC Symbol;Acc:HGNC:26098] ENSG00000011451 WIZ widely interspaced zinc finger motifs 0.018812736 [Source:HGNC Symbol;Acc:HGNC:30917] ENSG00000160888 IER2 immediate early response 2 0.018812736 [Source:HGNC Symbol;Acc:HGNC:28871] ENSG00000174807 CD248 CD248 molecule 0.018812736 [Source:HGNC Symbol;Acc:HGNC:18219] ENSG00000099821 POLRMT RNA polymerase mitochondrial 0.018832922 [Source:HGNC Symbol;Acc:HGNC:9200] ENSG00000211899 IGHM immunoglobulin heavy constant mu 0.018832922 [Source:HGNC Symbol;Acc:HGNC:5541] ENSG00000130313 PGLS 6-phosphogluconolactonase 0.019015294 [Source:HGNC Symbol;Acc:HGNC:8903] ENSG00000165702 GFI1B growth factor independent IB transcriptional repressor 0.019015294 [Source:HGNC Symbol;Acc:HGNC:4238] ENSG00000196557 CACNA1H calcium voltage-gated channel subunit alpha1 H 0.019108077 [Source:HGNC Symbol;Acc:HGNC:1395] ENSG00000188486 H2AFX H2A histone family member X 0.019120708 [Source:HGNC Symbol;Acc:HGNC:4739] ENSG00000103260 METRN “meteorin, glial cell differentiation regulator 0.01915234 [Source:HGNC Symbol;Acc:HGNC:14151]” ENSG00000166925 TSC22D4 TSC22 domain family member 4 0.01920241 [Source:HGNC Symbol;Acc:HGNC:21696] ENSG00000106266 SNX8 sorting nexin 8 0.019236897 [Source:HGNC Symbol;Acc:HGNC:14972] ENSG00000110400 NECTIN1 nectin cell adhesion molecule 1 0.01926502 [Source:HGNC Symbol;Acc:HGNC:9706] ENSG00000088992 TESC tescalcin 0.019687862 [Source:HGNC Symbol;Acc:HGNC:26065] ENSG00000126368 NR1D1 nuclear receptor subfamily 1 group D member 1 0.019740714 [Source:HGNC Symbol;Acc:HGNC:7962] ENSG00000103202 NME4 NME/NM23 nucleoside diphosphate kinase 4 0.019829586 [Source:HGNC Symbol;Acc:HGNC:7852] ENSG00000213626 LBH limb bud and heart development 0.019900152 [Source:HGNC Symbol;Acc:HGNC:29532] ENSG00000138629 UBL7 ubiquitin like 7 0.019916102 [Source:HGNC Symbol;Acc:HGNC:28221] ENSG00000254614 0.019916102 ENSG00000116521 SCAMP3s ecretory carrier membrane protein 3 0.019953714 [Source:HGNC Symbol;Acc:HGNC:10565] ENSG00000132481 TRIM47 tripartite motif containing 47 0.019989295 [Source:HGNC Symbol;Acc:HGNC:19020] ENSG00000105699 LSR lipolysis stimulated lipoprotein receptor 0.019999965 [Source:HGNC Symbol;Acc:HGNC:29572] ENSG00000125503 PPP1R12C protein phosphatase 1 regulatory subunit 12C 0.020063533 [Source:HGNC Symbol;Acc:HGNC:14947] ENSG00000103056 SMPD3 sphingomyelin phosphodiesterase 3 0.020115844 [Source:HGNC Symbol;Acc:HGNC:14240] ENSG00000156381 ANKRD9 ankyrin repeat domain 9 0.020225168 [Source:HGNC Symbol;Acc:HGNC:20096] ENSG00000197471 SPN sialophorin 0.020225168 [Source:HGNC Symbol;Acc:HGNC:11249] ENSG00000197471 SPN sialophorin 0.020225168 [Source:HGNC Symbol;Acc:HGNC:11249] ENSG00000063854 HAGH hydroxyacylglutathione hydrolase 0.020247513 [Source:HGNC Symbol;Acc:HGNC:4805] ENSG00000130590 SAMD10 sterile alpha motif domain containing 10 0.020258063 [Source:HGNC Symbol;Acc:HGNC:16129] ENSG00000167664 TMIGD2 transmembrane and immunoglobulin domain containing 2 0.020258063 [Source:HGNC Symbol;Acc:HGNC:28324] ENSG00000146083 RNF44 ring finger protein 44 0.020327471 [Source:HGNC Symbol;Acc:HGNC:19180] ENSG00000231925 TAPBP TAP binding protein 0.020387859 [Source:HGNC Symbol;Acc:HGNC:11566] ENSG00000198858 R3HDM4 R3H domain containing 4 0.020462672 [Source:HGNC Symbol;Acc:HGNC:28270] ENSG00000135924 DNAJB2 DnaJ heat shock protein family (Hsp40) member B2 0.020505106 [Source:HGNC Symbol;Acc:HGNC:5228] ENSG00000239732 TLR9 toll like receptor 9 0.02065324 [Source:HGNC Symbol;Acc:HGNC:15633] ENSG00000115268 RPS15 ribosomal protein S15 0.020839375 [Source:HGNC Symbol;Acc:HGNC:10388] ENSG00000108798 ABI3 ABI family member 3 0.02085252 [Source:HGNC Symbol;Acc:HGNC:29859] ENSG00000119669 IRF2BPL interferon regulatory factor 2 binding protein like 0.02099734 [Source:HGNC Symbol;Acc:HGNC:14282] ENSG00000160446 ZDHHC12 zinc finger DHHC-type containing 12 0.02150253 [Source:HGNC Symbol;Acc:HGNC:19159] ENSG00000063169 BICRA BRD4 interacting chromatin remodeling complex associated protein 0.021525887 [Source:HGNC Symbol;Acc:HGNC:4332] ENSG00000141933 TPGS1 tubulin polyglutamylase complex subunit 1 0.021539966 [Source:HGNC Symbol;Acc:HGNC:25058] ENSG00000088256 GNA11 G protein subunit alpha 11 0.021557835 [Source:HGNC Symbol;Acc:HGNC:4379] ENSG00000169583 CLIC3 chloride intracellular channel 3 0.021557835 [Source:HGNC Symbol;Acc:HGNC:2064] ENSG00000188511 C22orf34 chromosome 22 open reading frame 34 0.021557835 [Source:HGNC Symbol;Acc:HGNC:28010] ENSG00000165406 8-Mar membrane associated ring-CH-type finger 8 0.021577416 [Source:HGNC Symbol;Acc:HGNC:23356] ENSG00000173762 CD7 CD7 molecule 0.021879276 [Source:HGNC Symbol;Acc:HGNC:1695] ENSG00000188322 SBK1 SH3 domain binding kinase 1 0.021879276 [Source:HGNC Symbol;Acc:HGNC:17699] ENSG00000204310 AGPAT1 1-acylglycerol-3-phosphate O-acyltransferase 1 0.021879276 [Source:HGNC Symbol;Acc:HGNC:324] ENSG00000167797 CDK2AP2 cyclin dependent kinase 2 associated protein 2 0.021895705 [Source:HGNC Symbol;Acc:HGNC:30833] ENSG00000142669 SH3BGRL3 SH3 domain binding glutamate rich protein like 3 0.022007819 [Source:HGNC Symbol;Acc:HGNC:15568] ENSG00000155034 FBXL18 F-box and leucine rich repeat protein 18 0.022133956 [Source:HGNC Symbol;Acc:HGNC:21874] ENSG00000187840 EIF4EBP1 eukaryotic translation initiation factor 4E binding protein 1 0.02227554 [Source:HGNC Symbol;Acc:HGNC:3288] ENSG00000185187 SIGIRR single Ig and TIR domain containing 0.022615882 [Source:HGNC Symbol;Acc:HGNC:30575] ENSG00000158545 ZC3H18 zinc finger CCCH-type containing 18 0.022649486 [Source:HGNC Symbol;Acc:HGNC:25091] ENSG00000184730 APOBR polipoprotein B receptor 0.022689972 [Source:HGNC Symbol;Acc:HGNC:24087] ENSG00000204463 BAG6 BCL2 associated athanogene 6 0.022689972 [Source:HGNC Symbol;Acc:HGNC:13919] ENSG00000071242 RPS6KA2 ribosomal protein S6 kinase A2 0.022776502 [Source:HGNC Symbol;Acc:HGNC:10431] ENSG00000146701 MDH2 malate dehydrogenase 2 0.02289018 [Source:HGNC Symbol;Acc:HGNC:6971] ENSG00000180155 LYNX1 Ly6/neurotoxin 1 0.02289018 [Source:HGNC Symbol;Acc:HGNC:29604] ENSG00000213563 C8orf82 chromosome 8 open reading frame 82 0.023112388 [Source:HGNC Symbol;Acc:HGNC:33826] ENSG00000105281 SLC1A5 solute carrier family 1 member 5 0.023356543 [Source:HGNC Symbol;Acc:HGNC:10943] ENSG00000162882 HAAO “3-hydroxyanthranilate 3,4-dioxygenase 0.02337834 [Source:HGNC Symbol;Acc:HGNC:4796]” ENSG00000181513 ACBD4 acyl-CoA binding domain containing 4 0.02337834 [Source:HIGNC Symbol; Acc:HGNC:23337] ENSG00000185730 ZNF696 zinc finger protein 696 0.02337834 [Source:HGNC Symbol;Acc:HGNC:25872] ENSG00000007520 TSR3 “TSR3, acp transferase ribosome maturation factor 0.023637109 [Source:HGNC Symbol;Acc:HGNC:14175]” ENSG00000090006 LTBP4 latent transforming growth factor beta binding protein 4 0.023637109 [Source:HGNC Symbol;Acc:HGNC:6717] ENSG00000146535 GNA12 G protein subunit alpha 12 0.023652058 [Source:HIGNC Symbol; Acc:HGNC:4380] ENSG00000141965 FEM1A fem-1 homolog A 0.023707215 [Source:HGNC Symbol;Acc:HGNC:16934] ENSG00000160957 RECQL4 RecQ like helicase 4 0.023710452 [Source:HGNC Symbol;Acc:HGNC:9949] ENSG00000135916 ITM2C integral membrane protein 2C 0.023733416 [Source:HGNC Symbol;Acc:HGNC:6175] ENSG00000177732 SOX12 SRY-box 12 0.023733416 [Source:HGNC Symbol;Acc:HGNC:11198] ENSG00000184508 HDDC3 HD domain containing 3 0.023802652 [Source:HGNC Symbol;Acc:HGNC:30522] ENSG00000175591 P2RY2 purinergic receptor P2Y2 0.023918507 [Source:HGNC Symbol;Acc:HGNC:8541] ENSG00000127903 ZNF835 zinc finger protein 835 0.023926586 [Source:HGNC Symbol;Acc:HGNC:34332] ENSG00000176022 B3GALT6 “beta-1,3-galactosyltransferase 6 0.023926586 [Source:HGNC Symbol;Acc:HGNC:17978]” ENSG00000255319 ENPP7P8 ectonucleotide pyrophosphatase/phosphodiesterase 0.02392953 7 pseudogene 8 [Source:HGNC Symbol;Acc:HGNC:48691] ENSG00000105479 CCDC114 coiled-coil domain containing 114 0.02398767 [Source:HGNC Symbol;Acc:HGNC:26560] ENSG00000130529 TRPM4 transient receptor potential cation channel subfamily M member 4 0.024020687 [Source:HGNC Symbol;Acc:HGNC:17993] ENSG00000133250 ZNF414 zinc finger protein 414 0.024020687 [Source:HGNC Symbol;Acc:HGNC:20630] ENSG00000215908 CROCCP2 “ciliary rootlet coiled-coil, rootletin pseudogene 2 0.024052859 [Source:HGNC Symbol;Acc:HGNC:28170]” ENSG00000118046 STK11 serine/threonine kinase 11 0.024056107 [Source:HGNC Symbol;Acc:HGNC:11389] ENSG00000034152 MAP2K3 mitogen-activated protein kinase kinase 3 0.024155164 [Source:HGNC Symbol;Acc:HGNC:6843] ENSG00000142453 CARM1 coactivator associated arginine methyltransferase 1 0.024155164 [Source:HGNC Symbol;Acc:HGNC:23393] ENSG00000256323 NA NA 0.024155164 ENSG00000160094 ZNF362 zinc finger protein 362 0.024171066 [Source:HGNC Symbol;Acc:HGNC:18079] ENSG00000104884 ERCC2 “ERCC excision repair 2, TFIIH core complex helicase subunit 0.024345083 [Source:HGNC Symbol;Acc:HGNC:3434]” ENSG00000149257 SERPINH1 serpin family H member 1 0.024345083 [Source:HGNC Symbol;Acc:HGNC:1546] ENSG00000169635 HIC2 HIC ZBTB transcriptional repressor 2 0.024354637 [Source:HGNC Symbol;Acc:HGNC:18595] ENSG00000143416 SELENBP1 selenium binding protein 1 0.024421599 [Source:HGNC Symbol;Acc:HGNC:10719] ENSG00000148411 NACC2 NACC family member 2 0.02443315 [Source:HGNC Symbol;Acc:HGNC:23846] ENSG00000085872 CHERP calcium homeostasis endoplasmic reticulum protein 0.024463522 [Source:HGNC Symbol;Acc:HGNC:16930] ENSG00000176182 MYPOP “Myb related transcription factor, partner of profiling 0.024477311 [Source:HGNC Symbol;Acc:HGNC:20178]” ENSG00000160113 NR2F6 nuclear receptor subfamily 2 group F member 6 0.024505177 [Source:HGNC Symbol;Acc:HGNC:7977] ENSG00000108262 GIT1 GIT ArfGAP 1 0.024614621 [Source:HGNC Symbol;Acc:HGNC:4272] ENSG00000161395 PGAP3 post-GPI attachment to proteins 3 0.024705126 [Source:HGNC Symbol;Acc:HGNC:23719] ENSG00000142089 IFITM3 interferon induced transmembrane protein 3 0.024765171 [Source:HGNC Symbol;Acc:HGNC:5414] ENSG00000070444 MNT MAX network transcriptional repressor 0.025148395 [Source:HGNC Symbol;Acc:HGNC:7188] ENSG00000112514 CUTA cutA divalent cation tolerance homolog 0.025148395 [Source:HGNC Symbol;Acc:HGNC:21101] ENSG00000167394 ZNF668 zinc finger protein 668 0.025148395 [Source:HGNC Symbol;Acc:HGNC:25821] ENSG00000167965 MLST8 “MTOR associated protein, LST8 homolog 0.025148395 [Source:HGNC Symbol;Acc:HGNC:24825]” ENSG00000244187 TMEM141 transmembrane protein 141 0.025148395 [Source:HGNC Symbol;Acc:HGNC:28211] ENSG00000218175 0.02527518 ENSG00000110063 DCPS “decapping enzyme, scavenger 0.025300524 [Source:HGNC Symbol;Acc:HGNC:29812]” ENSG00000128805 ARHGAP22 Rho GTPase activating protein 22 0.025318552 [Source:HGNC Symbol;Acc:HGNC:30320] ENSG00000148400 NOTCH1 notch 1 0.025506427 [Source:HGNC Symbol;Acc:HGNC:7881] ENSG00000186076 0.0257616 ENSG00000167470 MIDN midnolin 0.02580767 [Source:HGNC Symbol;Acc:HGNC:16298] ENSG00000188305 PEAK3 PEAK family member 3 0.02580767 ENSG00000181396 OGFOD3 [Source:HGNC Symbol;Acc:HGNC:24793] 2-oxoglutarate and iron dependent oxygenase 0.026198035 domain containing 3 [Source:HGNC Symbol;Acc:HGNC:26174] ENSG00000240877 RN7SL521P “RNA, 7SL, cytoplasmic 521, pseudogene 0.026492508 [Source:HGNC Symbol;Acc:HGNC:46537]” ENSG00000130511 SSBP4 single stranded DNA binding protein 4 0.026588317 [Source:HGNC Symbol;Acc:HGNC:15676] ENSG00000063177 RPL18 ribosomal protein L18 0.026698079 [Source:HGNC Symbol;Acc:HGNC:10310] ENSG00000172663 TMEM134 transmembrane protein 134 0.026698079 [Source:HGNC Symbol;Acc:HGNC:26142] ENSG00000130706 ADRM1 adhesion regulating molecule 1 0.026721536 [Source:HGNC Symbol;Acc:HGNC:15759] ENSG00000214063 TSPAN4 tetraspanin 4 0.026759131 [Source:HGNC Symbol;Acc:HGNC:11859] ENSG00000161677 JOSD2 Josephin domain containing 2 0.026798474 [Source:HGNC Symbol;Acc:HGNC:28853] ENSG00000189060 H1F0 H1 histone family member 0 0.027109095 [Source:HGNC Symbol;Acc:HGNC:4714] ENSG00000256811 0.027109095 ENSG00000133317 LGALS12 galectin 12 0.027164347 [Source:HGNC Symbol;Acc:HGNC:15788] ENSG00000012061 ERCC1 “ERCC excision repair 1, endonuclease non-catalytic subunit 0.027196959 [Source:HGNC Symbol;Acc:HGNC:3433]” ENSG00000007376 RPUSD1 RNA pseudouridylate synthase domain containing 1 0.027275974 [Source:HGNC Symbol;Acc:HGNC:14173] ENSG00000108175 ZMIZ1 zinc finger MIZ-type containing 1 0.027331142 [Source:HGNC Symbol;Acc:HGNC:16493] ENSG00000132003 ZSWIM4 zinc finger SWIM-type containing 4 0.027331142 [Source:HGNC Symbol;Acc:HGNC:25704] ENSG00000148296 SURF6 surfeit 6 0.027362837 [Source:HGNC Symbol;Acc:HGNC:11478] ENSG00000186056 MATN1-AS1 MATN1 antisense RNA 1 0.02742002 [Source:HGNC Symbol;Acc:HGNC:40364] ENSG00000115649 CNPPD1 cyclin Pas1/PHO80 domain containing 1 0.027574972 [Source:HGNC Symbol;Acc:HGNC:25220] ENSG00000065057 NTHL1 nth like DNA glycosylase 1 0.027763734 [Source:HGNC Symbol;Acc:HGNC:8028] ENSG00000272098 NA NA 0.027825114 ENSG00000011009 LYPLA2 lysophospholipase II 0.028071412 [Source:HGNC Symbol;Acc:HGNC:6738] ENSG00000110025 SNX15 sorting nexin 15 0.028074538 [Source:HGNC Symbol;Acc:HGNC:14978] ENSG00000095321 CRAT carnitine O-acetyltransferase 0.028133383 [Source:HGNC Symbol;Acc:HGNC:2342] ENSG00000108515 ENO3 enolase 3 0.028133383 [Source:HGNC Symbol;Acc:HGNC:3354] ENSG00000123064 DDX54 DEAD-box helicase 54 0.028358899 [Source:HGNC Symbol;Acc:HGNC:20084] ENSG00000169564 PCBP1 poly(rC) binding protein 1 0.028645846 [Source:HGNC Symbol;Acc:HGNC:8647] ENSG00000171045 TSNARE1 t-SNARE domain containing 1 0.028645846 [Source:HGNC Symbol;Acc:HGNC:26437] ENSG00000225978 HAR1A highly accelerated region 1A (non-protein coding) 0.028645846 [Source:HGNC Symbol;Acc:HGNC:33117] ENSG00000128283 CDC42EP1 CDC42 effector protein 1 0.028675863 [Source:HGNC Symbol;Acc:HGNC:17014] ENSG00000174282 ZBTB4 zinc finger and BTB domain containing 4 0.028871519 [Source:HGNC Symbol;Acc:HGNC:23847] ENSG00000167685 ZNF444 zinc finger protein 444 0.028919683 [Source:HGNC Symbol;Acc:HGNC:16052] ENSG00000110104 CCDC86 coiled-coil domain containing 86 0.028929404 [Source:HGNC Symbol;Acc:HGNC:28359] ENSG00000171703 TCEA2 transcription elongation factor A2 0.029117009 [Source:HGNC Symbol;Acc:HGNC:11614] ENSG00000177600 RPLP2 ribosomal protein lateral stalk subunit P2 0.029298722 [Source:HGNC Symbol;Acc:HGNC:10377] ENSG00000182095 TNRC18 trinucleotide repeat containing 18 0.029299181 [Source:HGNC Symbol;Acc:HGNC:11962] ENSG00000167106 FAM102A family with sequence similarity 102 member A 0.029415219 [Source:HGNC Symbol;Acc:HGNC:31419] ENSG00000126458 RRAS RAS related 0.02952737 [Source:HGNC Symbol;Acc:HGNC:10447] ENSG00000105063 PPP6R1 protein phosphatase 6 regulatory subunit 1 0.02959944 [Source:HGNC Symbol;Acc:HGNC:29195] ENSG00000125730 C3 complement C3 0.029997906 [Source:HGNC Symbol;Acc:HGNC:1318] ENSG00000237973 MTCO1P12 mitochondrially encoded cytochrome c oxidase l pseudogene 12 0.030144659 [Source:HGNC Symbol;Acc:HGNC:52014] ENSG00000267412 0.030144659 ENSG00000185813 PCYT2 “phosphate cytidylyltransferase 2, ethanolamine 0.030317293 [Source:HGNC Symbol;Acc:HGNC:8756]” ENSG00000163462 TRIM46 tripartite motif containing 46 0.030614393 [Source:HGNC Symbol;Acc:HGNC:19019] ENSG00000157933 SKI SKI proto-oncogene 0.030701411 [Source:HGNC Symbol;Acc:HGNC:10896] ENSG00000161091 MFSD12 major facilitator superfamily domain containing 12 0.030704292 [Source:HGNC Symbol;Acc:HGNC:28299] ENSG00000185163 DDX51 DEAD-box helicase 51 0.030735268 [Source:HGNC Symbol;Acc:HGNC:20082] ENSG00000171813 PWWP2B PWWP domain containing 2B 0.030810478 [Source:HGNC Symbol;Acc:HGNC:25150] ENSG00000137267 TUBB2A tubulin beta 2A class Ila 0.030847037 [Source:HGNC Symbol;Acc:HGNC:12412] ENSG00000188747 NOXA1 NADPH oxidase activator 1 0.030853611 [Source:HGNC Symbol;Acc:HGNC:10668] ENSG00000108557 RAI1 retinoic acid induced 1 0.030977697 [Source:HGNC Symbol;Acc:HGNC:9834] ENSG00000137166 FOXP4 forkhead box P4 0.030977697 [Source:HGNC Symbol;Acc:HGNC:20842] ENSG00000204420 MPIG6B megakaryocyte and platelet inhibitory receptor G6b 0.031369168 [Source:HGNC Symbol;Acc:HGNC:13937] ENSG00000133265 HSPBP1 HSPA (Hsp70) binding protein 1 0.031442624 [Source:HGNC Symbol;Acc:HGNC:24989] ENSG00000008710 PKD1 “polycystin l, transient receptor potential channel interacting 0.031566582 [Source:HGNC Symbol;Acc:HGNC:9008]” ENSG00000099624 ATP5F1D ATP synthase Fl subunit delta 0.031657927 [Source:HGNC Symbol;Acc:HGNC:837] ENSG00000108819 PPP1R9B protein phosphatase 1 regulatory subunit 9B 0.031695534 [Source:HGNC Symbol;Acc:HGNC:9298] ENSG00000158292 GPR153 G protein-coupled receptor 153 0.031750316 [Source:HGNC Symbol;Acc:HGNC:23618] ENSG00000130382 MLLT1 “MLLT1, super elongation complex subunit 0.031828022 [Source:HGNC Symbol;Acc:HGNC:7134]” ENSG00000269352 PTOV1-AS2 PTOV1 antisense RNA 2 0.031850457 [Source:HGNC Symbol;Acc:HGNC:51284] ENSG00000162585 FAAP20 Fanconi anemia core complex associated protein 20 0.0320507 [Source:HGNC Symbol;Acc:HGNC:26428] ENSG00000157240 FZD1 frizzled class receptor 1 0.032151732 [Source:HGNC Symbol;Acc:HGNC:4038] ENSG00000135736 CCDC102A coiled-coil domain containing 102A 0.032302006 [Source:HGNC Symbol;Acc:HGNC:28097] ENSG00000020181 ADGRA2 adhesion G protein-coupled receptor A2 0.032424937 [Source:HGNC Symbol;Acc:HGNC:17849] ENSG00000198546 ZNF511 zinc finger protein 511 0.032576231 [Source:HGNC Symbol;Acc:HGNC:28445] ENSG00000123144 TRIR telomerase RNA component interacting RNase 0.032671184 [Source:HGNC Symbol;Acc:HGNC:28424] ENSG00000156860 FBRS fibrosin 0.032671184 [Source:HGNC Symbol;Acc:HGNC:20442] ENSG00000162910 MRPL55 mitochondrial ribosomal protein L55 0.032697662 [Source:HGNC Symbol;Acc:HGNC:16686] ENSG00000130731 METTL26 methyltransferase like 26 0.032833764 [Source:HGNC Symbol;Acc:HGNC:14141] ENSG00000101986 ABCD1 ATP binding cassette subfamily D member 1 0.032886018 [Source:HGNC Symbol;Acc:HGNC:61] ENSG00000020633 RUNX3 runt related transcription factor 3 0.033016587 [Source:HGNC Symbol;Acc:HGNC:10473] ENSG00000184640 9-Sep septin 9 0.033101928 [Source:HGNC Symbol;Acc:HGNC:7323] ENSG00000260521 NA NA 0.033101928 ENSG00000125787 GNRH2 gonadotropin releasing hormone 2 0.033349502 [Source:HGNC Symbol;Acc:HGNC:4420] ENSG00000229391 HLA-DRB6 “major histocompatibility complex, class 11, DR beta 6 (pseudogene) 0.033349502 [Source:HGNC Symbol;Acc:HGNC:4954]” ENSG00000160223 ICOSLG inducible T cell costimulator ligand 0.033394348 [Source:HGNC Symbol;Acc:HGNC:17087] ENSG00000105204 DYRK1B dual specificity tyrosine phosphorylation regulated kinase 1B 0.033465567 [Source:HGNC Symbol;Acc:HGNC:3092] ENSG00000142173 COL6A2 collagen type VI alpha 2 chain 0.033483825 [Source:HGNC Symbol;Acc:HGNC:2212] ENSG00000169710 FASN fatty acid synthase 0.033483825 [Source:HGNC Symbol;Acc:HGNC:3594] ENSG00000176533 GNG7 G protein subunit gamma 7 0.033483825 [Source:HGNC Symbol;Acc:HGNC:4410] ENSG00000179253 0.033483825 ENSG00000169972 PUSL1 pseudouridylate synthase-like 1 0.033509544 [Source:HGNC Symbol;Acc:HGNC:26914] ENSG00000160360 GPSM1 G protein signaling modulator 1 0.033771567 [Source:HGNC Symbol;Acc:HGNC:17858] ENSG00000171159 C9orf16 chromosome 9 open reading frame 16 0.033853634 [Source:HGNC Symbol;Acc:HGNC:17823] ENSG00000215375 MYL5 myosin light chain 5 0.033853634 [Source:HGNC Symbol;Acc:HGNC:7586] ENSG00000105402 NAPA NSF attachment protein alpha 0.034044441 [Source:HGNC Symbol;Acc:HGNC:7641] ENSG00000038532 CLEC16A C-type lectin domain containing 16A 0.034108157 [Source:HGNC Symbol;Acc:HGNC:29013] ENSG00000165175 MID1IP1 MID1 interacting protein 1 0.03418982 [Source:HGNC Symbol;Acc:HGNC:20715] ENSG00000166947 EPB42 erythrocyte membrane protein band 4.2 0.03418982 [Source:HGNC Symbol;Acc:HGNC:3381] ENSG00000168286 THAP11 TH AP domain containing 11 0.03418982 [Source:HGNC Symbol;Acc:HGNC:23194] ENSG00000168476 REEP4 receptor accessory protein 4 0.034591261 [Source:HGNC Symbol;Acc:HGNC:26176] ENSG00000107521 HPS1 “HPS1, biogenesis of lysosomal organelles complex 3 subunit 1 0.034688533 [Source:HGNC Symbol;Acc:HGNC:5163]” ENSG00000267436 0.034821851 ENSG00000099991 CABIN1 calcineurin binding protein 1 0.034858474 [Source:HGNC Symbol;Acc:HGNC:24187] ENSG00000169718 DUS1L dihydrouridine synthase 1 like 0.034980702 [Source:HGNC Symbol;Acc:HGNC:30086] ENSG00000105325 FZR1 fizzy and cell division cycle 20 related 1 0.035034499 [Source:HGNC Symbol;Acc:HGNC:24824] ENSG00000167291 TBC1D16 TBC1 domain family member 16 0.035082388 [Source:HGNC Symbol;Acc:HGNC:28356] ENSG00000213399 0.035085538 ENSG00000175040 CHST2 carbohydrate sulfotransferase 2 0.035106231 [Source:HGNC Symbol;Acc:HGNC:1970] ENSG00000228544 CCDC183-AS1 CCDC183 antisense RNA 1 0.035154264 [Source:HGNC Symbol;Acc:HGNC:44105] ENSG00000167658 EEF2 eukaryotic translation elongation factor 2 0.03521308 [Source:HGNC Symbol;Acc:HGNC:3214] ENSG00000090238 YPEL3 yippee like 3 0.035223199 [Source:HGNC Symbol;Acc:HGNC:18327] ENSG00000172508 CARNS1 carnosine synthase 1 0.03555645 [Source:HGNC Symbol;Acc:HGNC:29268] ENSG00000173272 MZT2A mitotic spindle organizing protein 2A 0.035664739 [Source:HGNC Symbol;Acc:HGNC:33187] ENSG00000141522 ARHGDIA Rho GDP dissociation inhibitor alpha 0.03575577 [Source:HGNC Symbol;Acc:HGNC:678] ENSG00000149541 B3GAT3 “beta-l,3-glucuronyltransferase 3 0.03575577 [Source:HGNC Symbol;Acc:HGNC:923]” ENSG00000171206 TRIM8 tripartite motif containing 8 0.035790036 [Source:HGNC Symbol;Acc:HGNC:15579] ENSG00000027869 SH2D2A SH2 domain containing 2A 0.035871776 [Source:HGNC Symbol;Acc:HGNC:10821] ENSG00000149823 VPS51 “VPS51, GARP complex subunit 0.035906645 [Source:HGNC Symbol;Acc:HGNC:1172]” ENSG00000196355 NA NA 0.035938935 ENSG00000165804 ZNF219 zinc finger protein 219 0.035996581 [Source:HGNC Symbol;Acc:HGNC:13011] ENSG00000177542 SLC25A22 solute carrier family 25 member 22 0.035996581 [Source:HGNC Symbol;Acc:HGNC:19954] ENSG00000130202 NECTIN2 nectin cell adhesion molecule 2 0.036025366 [Source:HGNC Symbol;Acc:HGNC:9707] ENSG00000006638 TBXA2R thromboxane A2 receptor 0.036065767 [Source:HGNC Symbol;Acc:HGNC:11608] ENSG00000025770 NCAPH2 non-SMC condensin II complex subunit H2 0.036065767 [Source:HGNC Symbol;Acc:HGNC:25071] ENSG00000100316 RPL3 ribosomal protein L3 0.036065767 [Source:HGNC Symbol;Acc:HGNC:10332] ENSG00000110665 C11orf21 chromosome 11 open reading frame 21 0.036065767 [Source:HGNC Symbol;Acc:HGNC:13231] ENSG00000160445 ZER1 zyg-11 related cell cycle regulator 0.036065767 [Source:HGNC Symbol;Acc:HGNC:30960] ENSG00000173786 CNP “2′,3′-cyclic nucleotide 3′ phosphodiesterase 0.036065767 [Source:HGNC Symbol;Acc:HGNC:2158]” ENSG00000229368 0.036065767 ENSG00000160789 LMNA lamin A/C 0.036188381 [Source:HGNC Symbol;Acc:HGNC:6636] ENSG00000166189 HPS6 “HPS6, biogenesis of lysosomal organelles complex 2 subunit 3 0.036188381 [Source:HGNC Symbol;Acc:HGNC:18817]” ENSG00000261226 0.036342968 ENSG00000185049 NELFA negative elongation factor complex member A 0.036383164 [Source:HGNC Symbol;Acc:HGNC:12768] ENSG00000005882 PDK2 pyruvate dehydrogenase kinase 2 0.036423123 [Source:HGNC Symbol;Acc:HGNC:8810] ENSG00000163050 COQ8A coenzyme Q8A 0.036459828 [Source:HGNC Symbol;Acc:HGNC:16812] ENSG00000060138 YBX3 Y-box binding protein 3 0.03651176 [Source:HGNC Symbol;Acc:HGNC:2428] ENSG00000122971 ACADS acyl-CoA dehydrogenase short chain 0.036511776 [Source:HGNC Symbol;Acc:HGNC:90] ENSG00000205927 OLIG2 oligodendrocyte transcription factor 2 0.036582868 [Source:HGNC Symbol;Acc:HGNC:9398] ENSG00000092096 SLC22A17 solute carrier family 22 member 17 0.036619295 [Source:HGNC Symbol;Acc:HGNC:23095] ENSG00000090554 FLT3LG fms related tyrosine kinase 3 ligand 0.036780281 [Source:HGNC Symbol;Acc:HGNC:3766] ENSG00000078902 TOLLIP toll interacting protein 0.036796695 [Source:HGNC Symbol;Acc:HGNC:16476] ENSG00000136802 LRRC8A leucine rich repeat containing 8 VRAC subunit A 0.036860551 [Source:HGNC Symbol;Acc:HGNC:19027] ENSG00000236976 0.036972133 ENSG00000100908 EMC9 ER membrane protein complex subunit 9 0.037054085 [Source:HGNC Symbol;Acc:HGNC:20273] ENSG00000105364 MRPL4 mitochondrial ribosomal protein L4 0.03712252 [Source:HGNC Symbol;Acc:HGNC:14276] ENSG00000157184 CPT2 carnitine palmitoyltransferase 2 0.03712252 [Source:HGNC Symbol;Acc:HGNC:2330] ENSG00000168056 LTBP3 latent transforming growth factor beta binding protein 3 0.037135417 [Source:HGNC Symbol;Acc:HGNC:6716] ENSG00000196313 POM121 POM121 transmembrane nucleoporin 0.037140956 [Source:HGNC Symbol;Acc:HGNC:19702] ENSG00000170604 IRF2BP1 nterferon regulatory factor 2 binding protein 1 0.037222007 [Source:HGNC Symbol;Acc:HGNC:21728] ENSG00000110697 PITPNM1 phosphatidylinositol transfer protein membrane associated 1 0.037374978 [Source:HGNC Symbol;Acc:HGNC:9003] ENSG00000100348 TXN2 thioredoxin 2 0.037546969 [Source:HGNC Symbol;Acc:HGNC:17772] ENSG00000102007 PLP2 proteolipid protein 2 0.037630556 [Source:HGNC Symbol;Acc:HGNC:9087] ENSG00000132005 RFX1 regulatory factor XI 0.037671165 [Source:HGNC Symbol;Acc:HGNC:9982] ENSG00000141499 WRAP53 WD repeat containing antisense to TP53 0.037678229 [Source:HGNC Symbol;Acc:HGNC:25522] ENSG00000189114 BLOC1S3 biogenesis of lysosomal organelles complex 1 subunit 3 0.037963219 [Source:HGNC Symbol;Acc:HGNC:20914] ENSG00000123154 WDR83 WD repeat domain 83 0.038059131 [Source:HGNC Symbol;Acc:HGNC:32672] ENSG00000127663 KDM4B lysine demethylase 4B 0.038059131 [Source:HGNC Symbol;Acc:HGNC:29136] ENSG00000175274 TP53I11 tumor protein p53 inducible protein 11 0.038059131 [Source:HGNC Symbol;Acc:HGNC:16842] ENSG00000249115 HAUS5 HAUS augmin like complex subunit 5 0.038059131 [Source:HGNC Symbol;Acc:HGNC:29130] ENSG00000130764 LRRC47 leucine rich repeat containing 47 0.038286929 [Source:HGNC Symbol;Acc:HGNC:29207] ENSG00000176946 THAP4 THAP domain containing 4 0.038286929 [Source:HGNC Symbol;Acc:HGNC:23187] ENSG00000137497 NUMA1 nuclear mitotic apparatus protein 1 0.038678067 [Source:HGNC Symbol;Acc:HGNC:8059] ENSG00000143761 ARF1 ADP ribosylation factor 1 0.038678067 [Source:HGNC Symbol;Acc:HGNC:652] ENSG00000198931 APRT adenine phosphoribosyltransferase 0.038678067 [Source:HGNC Symbol;Acc:HGNC:626] ENSG00000186174 BCL9L B cell CLL/lymphoma 9 like 0.039375488 [Source:HGNC Symbol;Acc:HGNC:23688] ENSG00000104894 CD37 CD37 molecule 0.039523734 [Source:HGNC Symbol;Acc:HGNC:1666] ENSG00000235314 LINC00957 long intergenic non-protein coding RNA 957 0.039534059 [Source:HGNC Symbol;Acc:HGNC:22332] ENSG00000076864 RAP1GAP RAP1 GTPase activating protein 0.039534171 [Source:HGNC Symbol;Acc:HGNC:9858] ENSG00000179348 GATA2 GAT A binding protein 2 0.039644975 [Source:HGNC Symbol;Acc:HGNC:4171] ENSG00000223496 EXOSC6 exosome component 6 0.039646513 [Source:HGNC Symbol;Acc:HGNC:19055] ENSG00000174004 NRROS negative regulator of reactive oxygen species 0.039697731 [Source:HGNC Symbol;Acc:HGNC:24613] ENSG00000185736 ADARB2 “adenosine deaminase, RNA specific B2 (inactive) 0.039813584 [Source:HGNC Symbol;Acc:HGNC:227]” ENSG00000177595 PIDD1 p53-induced death domain protein 1 0.039841437 [Source:HGNC Symbol;Acc:HGNC:16491] ENSG00000114767 RRP9 “ribosomal RNA processing 9, U3 small nucleolar RNA binding protein 0.039852243 [Source:HGNC Symbol;Acc:HGNC:16829]” ENSG00000198336 MYL4 myosin light chain 4 0.040061329 [Source:HGNC Symbol;Acc:HGNC:7585] ENSG00000267427 NA NA 0.040061329 ENSG00000123159 GIPC1 GIPC PDZ domain containing family member 1 0.040207239 [Source:HGNC Symbol;Acc:HGNC:1226] ENSG00000139405 RITA1 RBPJ interacting and tubulin associated 1 0.040571361 [Source:HGNC Symbol;Acc:HGNC:25925] ENSG00000149929 HIRIP3 HIRA interacting protein 3 0.040590193 [Source:HGNC Symbol;Acc:HGNC:4917] ENSG00000198517 MAFK MAF bZIP transcription factor K 0.040590193 [Source:HGNC Symbol;Acc:HGNC:6782] ENSG00000164897 TMUB1 transmembrane and ubiquitin like domain containing 1 0.040938395 [Source:HGNC Symbol;Acc:HGNC:21709] ENSG00000070047 PHRF1 PHD and ring finger domains 1 0.041015111 [Source:HGNC Symbol;Acc:HGNC:24351] ENSG00000100403 ZC3H7B zinc finger CCCH-type containing 7B 0.041151359 [Source:HGNC Symbol;Acc:HGNC:30869] ENSG00000205147 NA NA 0.041207854 ENSG00000184470 TXNRD2 thioredoxin reductase 2 0.04134465 [Source:HGNC Symbol;Acc:HGNC:18155] ENSG00000103145 HCFC1R1 host cell factor Cl regulator 1 0.041366672 [Source:HGNC Symbol;Acc:HGNC:21198] ENSG00000087086 FTL ferritin light chain 0.041631474 [Source:HGNC Symbol;Acc:HGNC:3999] ENSG00000102870 ZNF629 zinc finger protein 629 0.041631474 [Source:HGNC Symbol;Acc:HGNC:29008] ENSG00000181444 ZNF467 zinc finger protein 467 0.041868067 [Source:HGNC Symbol;Acc:HGNC:23154] ENSG00000142444 TIMM29 translocase of inner mitochondrial membrane 29 0.041933219 [Source:HGNC Symbol;Acc:HGNC:25152] ENSG00000204252 HLA-DOA “major histocompatibility complex, class 11, DO alpha 0.041944166 [Source:HGNC Symbol;Acc:HGNC:4936]” ENSG00000224051 CPTP ceramide-1-phosphate transfer protein 0.041944166 [Source:HGNC Symbol;Acc:HGNC:28116] ENSG00000103253 HAGHL hydroxyacylglutathione hydrolase like 0.042027801 [Source:HGNC Symbol;Acc:HGNC:14177] ENSG00000011590 ZBTB32 zinc finger and BTB domain containing 32 0.042101327 [Source:HGNC Symbol;Acc:HGNC:16763] ENSG00000182566 CLEC4G C-type lectin domain family 4 member G 0.042114834 [Source:HGNC Symbol;Acc:HGNC:24591] ENSG00000244165 P2RY11 purinergic receptor P2Y11 0.042114834 [Source:HGNC Symbol;Acc:HGNC:8540] ENSG00000267275 0.042114834 ENSG00000173327 MAP3K11 mitogen-activated protein kinase kinase kinase 11 0.042395519 [Source:HGNC Symbol;Acc:HGNC:6850] ENSG00000149418 STU suppression of tumorigenicity 14 0.04243773 [Source:HGNC Symbol;Acc:HGNC:11344] ENSG00000112658 SRF serum response factor 0.042440717 [Source:HGNC Symbol;Acc:HGNC:11291] ENSG00000106003 LFNG LFNG O-fucosylpeptide 3-beta-N-acetylglucosaminyltransferase 0.042450091 [Source:HGNC Symbol;Acc:HGNC:6560] ENSG00000164896 FASTK Fas activated serine/threonine kinase 0.042450091 [Source:HGNC Symbol;Acc:HGNC:24676] ENSG00000196544 BORCS6 BLOC-1 related complex subunit 6 0.042514351 [Source:HGNC Symbol;Acc:HGNC:25939] ENSG00000134107 BHLHE40 basic helix-loop-helix family member e40 0.042517218 [Source:HGNC Symbol;Acc:HGNC:1046] ENSG00000151176 PLBD2 phospholipase B domain containing 2 0.042582368 [Source:HGNC Symbol;Acc:HGNC:27283] ENSG00000183397 C19orf71 chromosome 19 open reading frame 71 0.042902315 [Source:HGNC Symbol;Acc:HGNC:34496] ENSG00000105738 SIPA1L3 signal induced proliferation associated 1 like 3 0.043052047 [Source:HGNC Symbol;Acc:HGNC:23801] ENSG00000157353 FUK fucokinase 0.043381308 [Source:HGNC Symbol;Acc:HGNC:29500] ENSG00000126062 TMEM115 transmembrane protein 115 0.043382452 [Source:HGNC Symbol;Acc:HGNC:30055] ENSG00000179632 MAF1 “MAF1 homolog, negative regulator of RNA polymerase III 0.043386409 [Source:HGNC Symbol;Acc:HGNC:24966]” ENSG00000254910 0.043544967 ENSG00000073111 MCM2 minichromosome maintenance complex component 2 0.043556269 [Source:HGNC Symbol;Acc:HGNC:6944] ENSG00000105698 USF2 “upstream transcription factor 2, c-fos interacting 0.043737282 [Source:HGNC Symbol;Acc:HGNC:12594]” ENSG00000261043 0.043870446 ENSG00000078808 SDF4 stromal cell derived factor 4 0.043914575 [Source:HGNC Symbol;Acc:HGNC:24188] ENSG00000182154 MRPL41 mitochondrial ribosomal protein L41 0.044022575 [Source:HGNC Symbol;Acc:HGNC:14492] ENSG00000237476 LINC01637 long intergenic non-protein coding RNA 1637 0.044022575 [Source:HGNC Symbol;Acc:HGNC:52424] ENSG00000264577 0.044022575 ENSG00000160877 NACC1 nucleus accumbens associated 1 0.044046233 [Source:HGNC Symbol;Acc:HGNC:20967] ENSG00000162032 SPSB3 splA/ryanodine receptor domain and SOCS box containing 3 0.044046233 [Source:HGNC Symbol;Acc:HGNC:30629] ENSG00000123933 MXD4 MAX dimerization protein 4 0.044146857 [Source:HGNC Symbol;Acc:HGNC:13906] ENSG00000149260 CAPN5 calpain 5 0.044146857 [Source:HGNC Symbol; Acc:HGNC:1482] ENSG00000197324 LRP10 LDL receptor related protein 10 0.044146857 [Source:HGNC Symbol;Acc:HGNC:14553] ENSG00000128011 LRFN1 leucine rich repeat and fibronectin type III domain containing 1 0.044424476 [Source:HGNC Symbol;Acc:HGNC:29290] ENSG00000103126 AXIN1 axin 1 0.044490553 [Source:HGNC Symbol;Acc:HGNC:903] ENSG00000183134 PTGDR2 prostaglandin D2 receptor 2 0.044490553 [Source:HGNC Symbol;Acc:HGNC:4502] ENSG00000185905 C16orf54 chromosome 16 open reading frame 54 0.044574634 [Source:HGNC Symbol;Acc:HGNC:26649] ENSG00000185905 C16orf54 chromosome 16 open reading frame 54 0.044574634 [Source:HGNC Symbol;Acc:HGNC:26649] ENSG00000176974 SHMT1 serine hydroxymethyltransferase 1 0.044717969 [Source:HGNC Symbol;Acc:HGNC:10850] ENSG00000105327 BBC3 BCL2 binding component 3 0.044899327 [Source:HGNC Symbol;Acc:HGNC:17868] ENSG00000212123 PRR22 proline rich 22 0.044899327 [Source:HGNC Symbol;Acc:HGNC:28354] ENSG00000171798 KNDC1 kinase non-catalytic C-lobe domain containing 1 0.045139854 [Source:HGNC Symbol;Acc:HGNC:29374] ENSG00000073150 PANX2 pannexin 2 0.045237232 [Source:HGNC Symbol;Acc:HGNC:8600] ENSG00000126453 BCL2L12 BCL2 like 12 0.04527356 [Source:HGNC Symbol;Acc:HGNC:13787] ENSG00000159692 CTBP1 C-terminal binding protein 1 0.04527356 [Source:HGNC Symbol;Acc:HGNC:2494] ENSG00000105248 CCDC94 coiled-coil domain containing 94 0.045450088 [Source:HGNC Symbol;Acc:HGNC:25518] ENSG00000101220 C20orf27 chromosome 20 open reading frame 27 0.045474144 [Source:HGNC Symbol;Acc:HGNC:15873] ENSG00000188735 TMEM120B transmembrane protein 120B 0.045474144 [Source:HGNC Symbol;Acc:HGNC:32008] ENSG00000149476 TKFC triokinase and FMN cyclase 0.045497488 [Source:HGNC Symbol;Acc:HGNC:24552] ENSG00000100105 PATZ1 POZ/BTB and AT hook containing zinc finger 1 0.045500961 [Source:HGNC Symbol;Acc:HGNC:13071] ENSG00000136295 TTYH3 tweety family member 3 0.045528908 [Source:HGNC Symbol;Acc:HGNC:22222] ENSG00000104823 ECH1 enoyl-CoA hydratase 1 0.045555559 [Source:HGNC Symbol;Acc:HGNC:3149] ENSG00000167930 FAM234A family with sequence similarity 234 member A 0.045584551 [Source:HGNC Symbol;Acc:HGNC:14163] ENSG00000125505 MBOAT7 membrane bound O-acyltransferase domain containing 7 0.045601783 [Source:HGNC Symbol;Acc:HGNC:15505] ENSG00000136720 HS6ST1 heparan sulfate 6-O-sulfotransferase 1 0.045601783 [Source:HGNC Symbol;Acc:HGNC:5201] ENSG00000156853 ZNF689 zinc finger protein 689 0.045601783 [Source:HGNC Symbol;Acc:HGNC:25173] ENSG00000176108 CHMP6 charged multivesicular body protein 6 0.045601783 [Source:HGNC Symbol;Acc:HGNC:25675] ENSG00000205336 ADGRG1 adhesion G protein-coupled receptor G1 0.045601783 [Source:HGNC Symbol;Acc:HGNC:4512] ENSG00000186350 RXRA retinoid X receptor alpha 0.045691236 [Source:HGNC Symbol;Acc:HGNC:10477] ENSG00000164849 GPR146 G protein-coupled receptor 146 0.045781 [Source:HGNC Symbol;Acc:HGNC:21718] ENSG00000124313 IQSEC2 IQ motif and Sec 7 domain 2 0.045921742 [Source:HGNC Symbol;Acc:HGNC:29059] ENSG00000148341 SH3GLB2 “SH3 domain containing GRB2 like, endophilin B2 0.045931004 [Source:HGNC Symbol;Acc:HGNC:10834]” ENSG00000213654 GPSM3 G protein signaling modulator 3 0.045963746 [Source:HGNC Symbol;Acc:HGNC:13945] ENSG00000171219 CDC42BPG CDC42 binding protein kinase gamma 0.046017697 [Source:HGNC Symbol;Acc:HGNC:29829] ENSG00000125741 OPA3 “OPA3, outer mitochondrial membrane lipid metabolism regulator 0.046210538 [Source:HGNC Symbol;Acc:HGNC:8142]” ENSG00000089693 MLF2 myeloid leukemia factor 2 0.046269835 [Source:HGNC Symbol;Acc:HGNC:7126] ENSG00000267283 0.046536749 ENSG00000238164 TNFRSF14-AS1 TNFRSF14 antisense RNA 1 0.046584081 [Source:HGNC Symbol;Acc:HGNC:26966] ENSG00000167815 PRDX2 peroxiredoxin 2 0.046640005 [Source:HGNC Symbol;Acc:HGNC:9353] ENSG00000140564 FURIN “furin, paired basic amino acid cleaving enzyme 0.046653045 [Source:HGNC Symbol;Acc:HGNC:8568]” ENSG00000059122 FLYWCH1 FLYWCH-type zinc finger 1 0.046934685 [Source:HGNC Symbol;Acc:HGNC:25404] ENSG00000070423 RNF126 ring finger protein 126 0.047070015 [Source:HGNC Symbol;Acc:HGNC:21151] ENSG00000027847 B4GALT7 “beta-1,4-galactosyltransferase 7 0.047130774 [Source:HGNC Symbol;Acc:HGNC:930]” ENSG00000108518 PFN1 profilin 1 0.047157356 [Source:HGNC Symbol;Acc:HGNC:8881] ENSG00000110711 AIP aryl hydrocarbon receptor interacting protein 0.04721490 [Source:HGNC Symbol;Acc:HGNC:358] ENSG00000164068 RNF123 ring finger protein 123 0.047214902 [Source:HGNC Symbol;Acc:HGNC:21148] ENSG00000137216 TMEM63B transmembrane protein 63B 0.047244731 [Source:HGNC Symbol;Acc:HGNC:17735] ENSG00000179588 ZFPM1 “zinc finger protein, FOG family member 1 0.047461433 [Source:HGNC Symbol;Acc:HGNC:19762]” ENSG00000188070 C11or95 chromosome 11 open reading frame 95 0.047461433 [Source:HGNC Symbol;Acc:HGNC:28449] ENSG00000162722 TRIM58 tripartite motif containing 58 0.047475759 [Source:HGNC Symbol;Acc:HGNC:24150] ENSG00000068724 TTC7A tetratricopeptide repeat domain 7 A 0.0476766 [Source:HGNC Symbol;Acc:HGNC:19750] ENSG00000142227 EMP3 epithelial membrane protein 3 0.0476766 [Source:HGNC Symbol;Acc:HGNC:3335] ENSG00000159714 ZDHHC1 zinc finger DHHC-type containing 1 0.04772167 [Source:HGNC Symbol;Acc:HGNC:17916] ENSG00000196182 STK40 serine/threonine kinase 40 0.047779011 [Source:HGNC Symbol;Acc:HGNC:21373] ENSG00000099875 MKNK2 MAP kinase interacting serine/threonine kinase 2 0.047824795 [Source:HGNC Symbol;Acc:HGNC:7111] ENSG00000132514 CLEC10A C-type lectin domain containing 10A 0.047824795 [Source:HGNC Symbol;Acc:HGNC:16916] ENSG00000197982 C1orf122 chromosome 1 open reading frame 122 0.047824795 [Source:HGNC Symbol;Acc:HGNC:24789] ENSG00000204348 DXO decapping exoribonuclease 0.047913021 [Source:HGNC Symbol;Acc:HGNC:2992] ENSG00000259856 RAB43P1 RAB43 pseudogene 1 0.048194625 [Source:HGNC Symbol;Acc:HGNC:33153] ENSG00000103254 FAM173A family with sequence similarity 173 member A 0.048206847 [Source:HGNC Symbol;Acc:HGNC:14152] ENSG00000196453 ZNF777 zinc finger protein 777 0.048246269 [Source:HGNC Symbol;Acc:HGNC:22213] ENSG00000167173 C15orf39 chromosome 15 open reading frame 39 0.048259142 [Source:HGNC Symbol;Acc:HGNC:24497] ENSG00000172534 HCFC1 host cell factor Cl 0.04840783 [Source:HGNC Symbol;Acc:HGNC:4839] ENSG00000198804 MT-CO1 mitochondrially encoded cytochrome c oxidase I 0.048409706 [Source:HGNC Symbol;Acc:HGNC:7419] ENSG00000244486 SCARF2 scavenger receptor class F member 2 0.048617065 [Source:HGNC Symbol;Acc:HGNC:19869] ENSG00000125652 ALKBH7 alkB homolog 7 0.048746819 [Source:HGNC Symbol;Acc:HGNC:21306] ENSG00000176101 SSNA1 SS nuclear autoantigen 1 0.048934402 [Source:HGNC Symbol;Acc:HGNC:11321] ENSG00000129103 SUMF2 sulfatase modifying factor 2 0.048950286 [Source:HGNC Symbol;Acc:HGNC:20415] ENSG00000115756 HPCAL1 hippocalcin like 1 0.049011448 [Source:HGNC Symbol;Acc:HGNC:5145] ENSG00000243566 UPK3B uroplakin 3B 0.049012128 [Source:HGNC Symbol;Acc:HGNC:21444] ENSG00000149150 SLC43A1 solute carrier family 43 member 1 0.049128197 [Source:HGNC Symbol;Acc:HGNC:9225] ENSG00000103227 LMF1 lipase maturation factor 1 0.049193782 [Source:HGNC Symbol;Acc:HGNC:14154] ENSG00000271959 0.049311473 ENSG00000261222 0.049471704 ENSG00000126217 MCF2L MCF.2 cell line derived transforming sequence like 0.049648177 [Source:HGNC Symbol;Acc:HGNC:14576] ENSG00000104964 AES amino-terminal enhancer of split 0.049726662 [Source:HGNC Symbol;Acc:HGNC:307] ENSG00000127831 VIL1 villin 1 0.049726662 [Source:HGNC Symbol;Acc:HGNC:12690] ENSG00000169738 DCXR dicarbonyl and L-xylulose reductase 0.049760492 [Source:HGNC Symbol;Acc:HGNC:18985] ENSG00000086015 MAST2 microtubule associated serine/threonine kinase 2 0.04998097 [Source:HGNC Symbol;Acc:HGNC:19035]

TABLE 8 AC3 GENES Ensembl Symbol DescriptionScore/AUC ENSG00000251705 RNA5-8SP6 “RNA, 5.8S ribosomal pseudogene 6 5.29E−67 [Source:HGNC Symbol;Acc:HGNC:41960]” ENSG00000133110 POSTN periostin 1.78E−06 [Source:HGNC Symbol;Acc:HGNC:16953] ENSG00000142449 FBN3 fibrillin 3 2.85E−05 [Source:HGNC Symbol;Acc:HGNC:18794] ENSG00000183668 PSG9 pregnancy specific beta-1-glycoprotein 9 9.26E−05 [Source:HGNC Symbol;Acc:HGNC:9526] ENSG00000258628 0.000107247 ENSG00000260290 0.000163871 ENSG00000224367 OACYLP “O-acyltransferase like, pseudogene 0.000275943 [Source:HGNC Symbol;Acc:HGNC:44362]” ENSG00000108018 SORCS1 sortilin related VPS 10 domain containing receptor 1 [Source:HGNC Symbol;Acc:HGNC:16697] 0.000366056 ENSG00000135454 B4GALNT1 “beta-1,4-N-acetyl-galactosaminyltransferase 1 0.000429017 [Source:HGNC Symbol;Acc:HGNC:4117]” ENSG00000266172 NA NA 0.000574378 ENSG00000173769 TOPAZ1 testis and ovary specific PAZ domain containing 1 [Source:HGNC Symbol; Acc:HGNC:24746] 0.00059023 ENSG00000181378 CFAP65 cilia and flagella associated protein 65 [Source:HGNC Symbol;Acc:HGNC:25325] 0.000602774 ENSG00000174498 IGDCC3 immunoglobulin superfamily DCC subclass member 3 [Source:HGNC Symbol;Acc:HGNC:9700] 0.00062895 ENSG00000089116 LHX5 LIM homeobox 5 0.000639272 [Source:HGNC Symbol;Acc:HGNC:14216] ENSG00000161270 NPHS1 “NPHS1, nephrin 0.000697583 [Source:HGNC Symbol;Acc:HGNC:7908]” ENSG00000006210 CX3CL1 C—X3—C motif chemokine ligand 1 0.000730947 [Source:HGNC Symbol;Acc:HGNC:10647] ENSG00000249618 LINC02465 long intergenic non-protein coding RNA 2465 0.000730947 [Source:HGNC Symbol;Acc:HGNC:53403] ENSG00000253871 0.000789684 ENSG00000130540 SULT4A1 sulfotransferase family 4A member 1 0.000791019 [Source:HGNC Symbol;Acc:HGNC:14903] ENSG00000148942 SLC5A12 solute carrier family 5 member 12 0.000819378 [Source:HGNC Symbol;Acc:HGNC:28750] ENSG00000226790 HNRNPA3P1 heterogeneous nuclear ribonucleoprotein A3 pseudogene 1 0.000826721 [Source:HGNC Symbol;Acc:HGNC:13729] ENSG00000160460 SPTBN4 “spectrin beta, non-erythrocytic 4 0.000837162 [Source:HGNC Symbol; Acc:HGNC:14896]” ENSG00000243130 PSG11 pregnancy specific beta-1-glycoprotein 11 0.000837162 [Source:HGNC Symbol;Acc:HGNC:9516] ENSG00000244694 PTCHD4 patched domain containing 4 0.000837162 [Source:HGNC Symbol;Acc:HGNC:21345] ENSG00000249464 LINC01091 long intergenic non-protein coding RNA 1091 0.000837162 [Source:HGNC Symbol;Acc:HGNC:27721] ENSG00000011677 GABRA3 gamma-aminobutyric acid type A receptor alpha3 subunit 0.000896018 [Source:HGNC Symbol;Acc:HGNC:4077] ENSG00000256343 0.00097441 ENSG00000039139 DNAH5 dynein axonemal heavy chain 5 0.001236713 [Source:HGNC Symbol;Acc:HGNC:2950] ENSG00000130635 COL5A1 collagen type V alpha 1 chain 0.001236713 [Source:HGNC Symbol;Acc:HGNC:2209] ENSG00000242512 LINC01206 long intergenic non-protein coding RNA 1206 0.001253551 [Source:HGNC Symbol;Acc:HGNC:49637] ENSG00000164692 COL1A2 collagen type 1 alpha 2 chain 0.00126185 [Source:HGNC Symbol;Acc:HGNC:2198] ENSG00000259841 LINC01566 long intergenic non-protein coding RNA 1566 0.001274332 [Source:HGNC Symbol;Acc:HGNC:27555] ENSG00000170777 TPD52L3 tumor protein D52 like 3 0.001484087 [Source:HGNC Symbol;Acc:HGNC:23382] ENSG00000186487 MYT1L myelin transcription factor 1 like 0.001774703 [Source:HGNC Symbol;Acc:HGNC:7623] ENSG00000082175 PGR progesterone receptor 0.001879127 [Source:HGNC Symbol;Acc:HGNC:8910] ENSG00000205922 ONECUT3 one cut homeobox 3 0.001993667 [Source:HGNC Symbol;Acc:HGNC:13399] ENSG00000249341 0.002126073 ENSG00000139865 TTC6 tetratricopeptide repeat domain 6 0.002268239 [Source:HGNC Symbol;Acc:HGNC:19739] ENSG00000154478 GPR26 G protein-coupled receptor 26 0.002268239 [Source:HGNC Symbol;Acc:HGNC:4481] ENSG00000174358 SLC6A19 solute carrier family 6 member 19 0.002268239 [Source:HGNC Symbol;Acc:HGNC:27960] ENSG00000235711 ANKRD34C ankyrin repeat domain 34C 0.002268239 [Source:HGNC Symbol;Acc:HGNC:33888] ENSG00000170381 SEMA3E semaphorin 3E 0.002327494 [Source:HGNC Symbol;Acc:HGNC:10727] ENSG00000142611 PRDM16 PR/SET domain 16 0.002350766 [Source:HGNC Symbol;Acc:HGNC:14000] ENSG00000205396 LINC00661 long intergenic non-protein coding RNA 661 0.002366966 [Source:HGNC Symbol;Acc:HGNC:27002] ENSG00000253288 0.00239082 ENSG00000171435 KSR2 kinase suppressor of ras 2 0.002607962 [Source:HGNC Symbol;Acc:HGNC:18610] ENSG00000256616 0.002639596 ENSG00000171804 WDR87 WD repeat domain 87 0.002806683 [Source:HGNC Symbol;Acc:HGNC:29934] ENSG00000237125 HAND2-AS1 HAND2 antisense RNA 1 (head to head) 0.00289999 [Source:HGNC Symbol;Acc:HGNC:48872] ENSG00000240694 PNMA2 PNMA family member 2 0.002940811 [Source:HGNC Symbol;Acc:HGNC:9159] ENSG00000102452 NALCN sodium leak channel, non-selective 0.003094645 [Source:HGNC Symbol;Acc:HGNC:19082]” ENSG00000214929 SPATA31D1 SPATA31 subfamily D member 1 0.003264148 [Source:HGNC Symbol;Acc:HGNC:37283] ENSG00000115041 KCNIP3 potassium voltage-gated channel interacting protein 3 0.00328034 [Source:HGNC Symbol;Acc:HGNC;15523] ENSG00000185038 MROH2A maestro heat like repeat family member 2A 0.003313878 [Source:HGNC Symbol;Acc:HGNC:27936] ENSG00000138892 TTLL8 tubulin tyrosine ligase like 8 0.003497603 [Source:HGNC Symbol;Acc:HGNC:34000] ENSG00000147573 TRIM55 tripartite motif containing 55 0.003573936 [Source:HGNC Symbol;Acc:HGNC:14215] ENSG00000165323 FAT3 FAT atypical cadherin 3 0.003629544 [Source:HGNC Symbol;Acc:HGNC:23112] ENSG00000142623 PADI1 peptidyl arginine deiminase 1 0.003697796 [Source:HGNC Symbol;Acc:HGNC:18367] ENSG00000146521 LINC01558 long intergenic non-protein coding RNA 1558 0.003779666 [Source:HGNC Symbol;Acc:HGNC:21235] ENSG00000125255 SLC10A2 solute carrier family 10 member 2 0.003857127 [Source:HGNC Symbol;Acc:HGNC:10906] ENSG00000103855 CD276 CD276 molecule 0.004037668 [Source:HGNC Symbol;Acc:HGNC:19137] ENSG00000168907 PLA2G4F phospholipase A2 group IVF 0.00413675 [Source:HGNC Symbol;Acc:HGNC:27396] ENSG00000141668 CBLN2 cerebellin 2 precursor 0.004198501 [Source:HGNC Symbol;Acc:HGNC:1544] ENSG00000197991 0.004252179 ENSG00000149633 KIAA1755 KIAA1755 0.004331797 [Source:HGNC Symbol;Acc:HGNC:29372] ENSG00000157927 RADIL Rap associating with DIL domain 0.004332718 [Source:HGNC Symbol;Acc:HGNC:22226] ENSG00000138759 FRAS1 Fraser extracellular matrix complex subunit 1 0.004539725 [Source:HGNC Symbol;Acc:HGNC:19185] ENSG00000174963 ZIC4 Zic family member 4 0.004539725 [Source:HGNC Symbol;Acc:HGNC:20393] ENSG00000177551 NHLH2 nescient helix-loop-helix 2 0.004560802 [Source:HGNC Symbol;Acc:HGNC:7818] ENSG00000250230 0.004576049 ENSG00000204929 0.00461274 ENSG00000163975 MELTF melanotransferrin 0.004655716 [Source:HGNC Symbol;Acc:HGNC:7037] ENSG00000095587 TLL2 tolloid like 2 0.004686524 [Source:HGNC Symbol;Acc:HGNC:11844] ENSG00000221826 PSG3 pregnancy specific beta-1-glycoprotein 3 0.004686524 [Source:HGNC Symbol;Acc:HGNC:9520] ENSG00000105392 CRX cone-rod homeobox 0.004730282 [Source:HGNC Symbol;Acc:HGNC:2383] ENSG00000188338 SLC38A3 solute carrier family 38 member 3 0.004737254 [Source:HGNC Symbol;Acc:HGNC:18044] ENSG00000167654 ATCAY “ATCAY, caytaxin 0.004891089 [Source:HGNC Symbol;Acc:HGNC:779]” ENSG00000177511 ST8SIA3 “STA8 alpha-N-acetyl-neuraminide alpha-2,8-sialytransferase 3 0.00498476 [Source:HGNC Symbol;Acc:HGNC:14269]” ENSG00000215895 0.005091461 ENSG00000124466 LYPD3 LY6/PLAUR domain containing 3 0.005118791 [Source:HGNC Symbol;Acc:HGNC:24880] ENSG00000084636 COL16A1 collagen type XVI alpha 1 chain 0.00516436 [Source:HGNC Symbol;Acc:HGNC:2193] ENSG00000104537 ANXA13 annexin A13 0.005166641 [Source:HGNC Symbol;Acc:HGNC:536] ENSG00000145526 CDH18 cadherin 18 0.005245896 [Source:HGNC Symbol;Acc:HGNC:1757] ENSG00000161103 0.005294938 ENSG00000168484 SFTPC surfactant protein C 0.005473496 [Source:HGNC Symbol;Acc:HGNC:10802] ENSG00000188886 ASTL astacin like metalloendopeptidase 0.005530506 [Source:HGNC Symbol;Acc:HGNC:31704] ENSG00000198765 SYCP1 synaptonemal complex protein 1 0.005554714 [Source:HGNC Symbol;Acc:HGNC:11487] ENSG00000234177 LINC01114 long intergenic non-protein coding RNA 1114 0.005808942 [Source:HGNC Symbol;Acc:HGNC:49245] ENSG00000091656 ZFHX4 zinc finger homeobox 4 0.005809417 [Source:HGNC Symbol;Acc:HGNC:30939] ENSG00000151572 ANO4 anoctamin 4 0.005857886 [Source:HGNC Symbol;Acc:HGNC:23837] ENSG00000178965 ERICH3 glutamate rich 3 0.005890875 [Source:HGNC Symbol;Acc:HGNC:25346] ENSG00000248587 GDNF-AS1 GDNF antisense RNA 1 (head to head) 0.005890875 [Source:HGNC Symbol;Acc:HGNC:43592] ENSG00000144908 ALDH1L1 aldehyde dehydrogenase 1 family member L1 0.006015103 [Source:HGNC Symbol;Acc:HGNC:3978] ENSG00000152822 GRM1 glutamate metabotropic receptor 1 0.006033529 [Source:HGNC Symbol;Acc:HGNC:4593] ENSG00000138675 FGF5 fibroblast growth factor 5 0.006101348 [Source:HGNC Symbol;Acc:HGNC:3683] ENSG00000187772 LIN28B lin-28 homolog B 0.006111478 [Source:HGNC Symbol;Acc:HGNC:32207] ENSG00000227471 AKR1B15 aldo-keto reductase family 1 member B15 0.006366933 [Source:HGNC Symbol;Acc:HGNC:37281] ENSG00000174502 SLC26A9 solute carrier family 26 member 9 0.006716425 [Source:HGNC Symbol;Acc:HGNC:14469] ENSG00000078549 ADCYAP1R1 ADCYAP receptor type 1 0.006848491 [Source:HGNC Symbol;Acc:HGNC:242] ENSG00000159650 UROC1 urocanate hydratase 1 0.006848491 [Source:HGNC Symbol;Acc:HGNC:26444] ENSG00000217094 PPIAP31 peptidylprolyl isomerase A pseudogene 31 0.006866623 [Source:HGNC Symbol;Acc:HGNC:44962] ENSG00000006128 TAC1 tachykinin precursor 1 0.006929673 [Source:HGNC Symbol;Acc:HGNC:11517] ENSG00000158077 NLRP14 NLR family pyrin domain containing 14 0.006952696 [Source:HGNC Symbol;Acc:HGNC:22939] ENSG00000223414 LINC00473 long intergenic non-protein coding RNA 473 0.006952696 [Source:HGNC Symbol;Acc:HGNC:21160] ENSG00000144488 ESPNL espin like ENSG00000144730 IL17RD interleukin 17 receptor D 0.007141116 [Source:HGNC Symbol;Acc:HGNC:17616] ENSG00000137819 PAQR5 progestin and adipoQ receptor family member 5 0.007179081 [Source:HGNC Symbol;Acc:HGNC:29645] ENSG00000162631 NTNG1 netrin G1 0.007255358 [Source:HGNC Symbol;Acc:HGNC:23319] ENSG00000185974 GRK1 G protein-coupled receptor kinase 1 0.007327997 [Source:HGNC Symbol;Acc:HGNC:10013] ENSG00000261275 0.007327997 ENSG00000249267 LINC00939 long intergenic non-protein coding RNA 939 [Source:HGNC Symbol;Acc:HGNC:48631] 0.007349367 ENSG00000227827 ENSG00000100065 CARD10 capase recruitment domain family member 10 0.007527421 [Source:HGNC Symbol;Acc:HGNC:16422] ENSG00000119125 GDA guanine deaminase 0.007619923 [Source:HGNC Symbol;Acc:HGNC:4212] ENSG00000106304 SPAM1 sperm adhesion molecule 1 0.00781679 [Source:HGNC Symbol;Acc:HGNC:11217] ENSG00000250493 0.007835589 ENSG00000158258 CLSTN2 calsyntenin 2 [Source:HGNC Symbol;Acc:HGNC:17448] 0.008149414 ENSG00000175329 ISX intestine specific homeobox [Source:HGNC Symbol;Acc:HGNC:28084] 0.008233566 ENSG00000188488 SERPINA5 serpin family A member 5 [Source:HGNC Symbol;Acc:HGNC:8723] 0.008534971 ENSG00000249584 LINC02225 long intergenic non-protein coding RNA 2225 0.00866593 Source:HGNC Symbol;Acc:HGNC:53094] ENSG00000147655 RSPO2 R-spondin 2 0.008823914 [Source:HGNC Symbol;Acc:HGNC:28583] ENSG00000171587 DSCAM DS cell adhesion molecule 0.008841283 [Source:HGNC Symbol;Acc:HGNC:3039] ENSG00000120738 EGR1 early growth response 1 0.008960131 [Source:HGNC Symbol;Acc:HGNC:3238] ENSG00000127129 EDN2 endothelin 2 0.009244272 [Source:HGNC Symbol;Acc:HGNC:3177] ENSG00000157423 HYDIN “HYDIN, axonemal central pair apparatus protein 0.009244272 [Source:HGNC Symbol;Acc:HGNC:19368]” ENSG00000196565 HBG2 hemoglobin subunit gamma 2 0.009327518 [Source:HGNC Symbol;Acc:HGNC:4832] ENSG00000235881 0.009327518 ENSG00000111262 KCNA1 potassium voltage-gated channel subfamily A member 1 0.009418575 [Source:HGNC Symbol;Acc:HGNC:6218] ENSG00000187527 ATP13A5 ATPase 13A5 0.009514824 [Source:HGNC Symbol;Acc:HGNC:31789] ENSG00000188803 SHISA6 shisa family member 6 0.009514824 [Source:HGNC Symbol;Acc:HGNC:34491] ENSG00000175535 PNLIP pancreatic lipase 0.009619326 [Source:HGNC Symbol;Acc:HGNC:9155] ENSG00000225953 SATB2-AS1 SATB2 antisense RNA 1 0.009647997 [Source:HGNC Symbol;Acc:HGNC:26490] ENSG00000136695 IL36RN interleukin 36 receptor antagonist 0.009810065 [Source:HGNC Symbol;Acc:HGNC:15561] ENSG00000259790 ANP32BP1 acidic nuclear phosphoprotein 32 family member B pseudogene 1 0.009820284 [Source:HGNC Symbol;Acc:HGNC:24267] ENSG00000225813 0.009894409 ENSG00000179008 C14orf39 chromosome 14 open reading frame 39 0.009896903 [Source:HGNC Symbol;Acc:HGNC:19849] ENSG00000150893 FREM2 FRAS1 related extracellular matrix protein 2 0.009945757 [Source:HGNC Symbol;Acc:HGNC:25396] ENSG00000197079 KRT35 keratin 35 0.009945757 [Source:HGNC Symbol;Acc:HGNC:6453] ENSG00000231131 LINC01468 long intergenic non-protein coding RNA 1468 0.010123625 [Source:HGNC Symbol;Acc:HGNC:50913] ENSG00000268388 FENDRR FOXF1 adjacent non-coding developmental regulatory RNA 0.010151023 [Source:HGNC Symbol;Acc:HGNC:43894] ENSG00000159251 ACTC1 “actin, alpha, cardiac muscle 1 0.010212535 [Source:HGNC Symbol;Acc:HGNC:143]” ENSG00000158125 XDH xanthine dehydrogenase 0.010258334 [Source:HGNC Symbol;Acc:HGNC:12805] ENSG00000156222 SLC28A1 solute carrier family 28 member 1 0.010392835 [Source:HGNC Symbol;Acc:HGNC:11001] ENSG00000260759 0.010741484 ENSG00000110975 SYT10 synaptotagmin 10 0.010787993 [Source:HGNC Symbol;Acc:HGNC:19266] ENSG00000186185 KIF18B kinesin family member 18B 0.010844893 [Source:HGNC Symbol;Acc:HGNC:27102] ENSG00000110887 DAO D-amino acid oxidase 0.011064297 [Source:HGNC Symbol;Acc:HGNC:2671] ENSG00000132297 HHLA1 HERV-H LTR-associating 1 0.011064297 [Source:HGNC Symbol;Acc:HGNC:4904] ENSG00000146839 ZAN zonadhesin (gene/pseudogene) 0.011064297 [Source:HGNC Symbol;Acc:HGNC:12857] ENSG00000215864 NBPF7 NBPF member 7 0.01113278 [Source:HGNC Symbol;Acc:HGNC:31989] ENSG00000233395 LINC00841 long intergenic non-protein coding RNA 841 0.011213055 [Source:HGNC Symbol;Acc:HGNC:27430] ENSG00000177354 C10orf71 chromosome 10 open reading frame 71 0.011268372 [Source:HGNC Symbol;Acc:HGNC:26973] ENSG00000148357 HMCN2 hemicentin 2 0.01150342 [Source:HGNC Symbol;Acc:HGNC:21293] ENSG00000215405 NA NA 0.011599767 ENSG00000203900 0.011732314 ENSG00000218672 0.011732314 ENSG00000261104 0.011732314 ENSG00000123243 ITIH5 inter-alpha-trypsin inhibitor heavy chain family member 5 0.011851589 [Source:HGNC Symbol;Acc:HGNC:21449] ENSG00000213467 HMGB1P37 high mobility group box 1 pseudogene 37 0.011876979 [Source:HGNC Symbol;Acc:HGNC:39184] ENSG00000119283 TRIM67 tripartite motif containing 67 0.011900585 [Source:HGNC Symbol;Acc:HGNC:31859] ENSG00000166984 TCP10L2 t-complex 10 like 2 0.012009181 [Source:HGNC Symbol;Acc:HGNC:21254] ENSG00000204941 PSG5 pregnancy specific beta-1-glycoprotein 5 0.012022323 [Source:HGNC Symbol;Acc:HGNC:9522] ENSG00000230552 0.012137266 ENSG00000115155 OTOF otoferlin 0.012228668 [Source:HGNC Symbol;Acc:HGNC:8515] ENSG00000163395 IGFN1 immunoglobulin-like and fibronectin type III domain containing 1 0.012230791 [Source:HGNC Symbol;Acc:HGNC:24607] ENSG00000122778 KIAA1549 KIAA1549 0.012393242 [Source:HGNC Symbol;Acc:HGNC:22219] ENSG00000169169 CPT1C carnitine palmitoyltransferase IC 0.012437719 [Source:HGNC Symbol;Acc:HGNC:18540] ENSG00000160994 CCDC105 coiled-coil domain containing 105 0.012486932 [Source:HGNC Symbol;Acc:HGNC:26866] ENSG00000237515 SHISA9 shisa family member 9 0.012486932 ENSG00000105605 CACNG7 [Source:HGNC Symbol;Acc:HGNC:37231] calcium voltage-gated channel auxiliary subunit gamma 7 0.012676606 [Source:HGNC Symbol;Acc:HGNC:13626] ENSG00000185739 SRL sarcalumenin 0.012676606 [Source:HGNC Symbol;Acc:HGNC:11295] ENSG00000101680 LAMA1 laminin subunit alpha l [Source:HGNC Symbol;Acc:HGNC:6481] ENSG00000240021 TEX35 testis expressed 35 0.012795538 [Source:HGNC Symbol;Acc:HGNC:25366] ENSG00000250423 KIAA1210 KIAA1210 0.012935817 [Source:HGNC Symbol;Acc:HGNC:29218] ENSG00000198788 MUC2 “mucin 2, oligomeric mucus/gel-forming 0.012968601 [Source:HGNC Symbol;Acc:HGNC:7512]” ENSG00000205312 KRT17P4 keratin 17 pseudogene 4 0.013016002 [Source:HGNC Symbol;Acc:HGNC:50722] ENSG00000214128 TMEM213 transmembrane protein 213 0.013016002 [Source:HGNC Symbol;Acc:HGNC:27220] ENSG00000178568 ERBB4 erb-b2 receptor tyrosine kinase 4 0.013045986 [Source:HGNC Symbol;Acc:HGNC:3432] ENSG00000175084 DES desmin 0.013296119 [Source:HGNC Symbol;Acc:HGNC:2770] ENSG00000078295 ADCY2 adenylate cyclase 2 0.013400191 [Source:HGNC Symbol;Acc:HGNC:233] ENSG00000132639 SNAP25 synaptosome associated protein 25 0.013440348 [Source:HGNC Symbol;Acc:HGNC:11132] ENSG00000187094 CCK cholecystokinin 0.013447765 [Source:HGNC Symbol;Acc:HGNC:1569] ENSG00000018625 ATP1A2 ATPase Na+/K+ transporting subunit alpha 2 0.013509365 [Source:HGNC Symbol;Acc:HGNC:800] ENSG00000168542 COL3A1 collagen type III alpha 1 chain 0.013843652 [Source:HGNC Symbol;Acc:HGNC:2201] ENSG00000239921 LINC01471 long intergenic non-protein coding RNA 1471 0.013848913 [Source:HGNC Symbol;Acc:HGNC:51106] ENSG00000233183 0.013964273 ENSG00000167798 C3P1 complement component 3 precursor pseudogene 0.013987555 [Source:HGNC Symbol;Acc:HGNC:34414] ENSG00000183778 B3GALT5 “beta-1,3-galactosyltransferase 5 0.01405326 [Source:HGNC Symbol;Acc:HGNC:920]” ENSG00000168481 LGI3 leucine rich repeat LGI family member 3 0.014132769 [Source:HGNC Symbol;Acc:HGNC:18711] ENSG00000227744 LINC01940 long intergenic non-protein coding RNA 1940 0.014149077 [Source:HGNC Symbol;Acc:HGNC:52763] ENSG00000138162 TACC2 transforming acidic coiled-coil containing protein 2 0.014184675 [Source:HGNC Symbol;Acc:HGNC:11523] ENSG00000250049 0.014522615 ENSG00000236445 LINC00608 long intergenic non-protein coding RNA 608 0.014606813 Source:HGNC Symbol;Acc:HGNC:27179] ENSG00000165966 PDZRN4 PDZ domain containing ring finger 4 0.014749092 [Source:HGNC Symbol;Acc:HGNC:30552] ENSG00000169876 MUC17 “mucin 17, cell surface associated 0.014749092 [Source:HGNC Symbol;Acc:HGNC:16800]” ENSG00000078898 BPIFB2 BPI fold containing family B member 2 0.014831419 [Source:HGNC Symbol;Acc:HGNC:16177] ENSG00000130528 HRC histidine rich calcium binding protein 0.014902982 [Source:HGNC Symbol;Acc:HGNC:5178] ENSG00000111799 COL12A1 collagen type XII alpha 1 chain 0.015069239 [Source:HGNC Symbol;Acc:HGNC:2188] ENSG00000185303 SFTPA2 surfactant protein A2 0.015347263 [Source:HGNC Symbol;Acc:HGNC:10799] ENSG00000146648 EGFR epidermal growth factor receptor 0.015466899 [Source:HGNC Symbol;Acc:HGNC:3236] ENSG00000205592 MUC19 “mucin 19, oligomeric 0.015539471 [Source:HGNC Symbol;Acc:HGNC:14362]” ENSG00000198597 ZNF536 zinc finger protein 536 0.015552452 [Source:HGNC Symbol;Acc:HGNC:29025] ENSG00000120332 TNN tenascin N 0.015559411 [Source:HGNC Symbol;Acc:HGNC:22942] ENSG00000197406 DIO3 iodothyronine deiodinase 3 0.015755832 [Source:HGNC Symbol;Acc:HGNC:2885] ENSG00000204283 LINC01973 long intergenic non-protein coding RNA 1973 0.015755832 [Source:HGNC Symbol;Acc:HGNC:52800] ENSG00000151224 MAT1A methionine adenosyltransferase 1A 0.015829354 [Source:HGNC Symbol;Acc:HGNC:6903] ENSG00000257008 GPR142 G protein-coupled receptor 142 0.015942034 [Source:HGNC Symbol;Acc:HGNC:20088] ENSG00000139220 PPFIA2 PTPRF interacting protein alpha 2 0.015986308 [Source:HGNC Symbol;Acc:HGNC:9246] ENSG00000141946 ZIM3 zinc finger imprinted 3 0.015986308 [Source:HGNC Symbol;Acc:HGNC:16366] ENSG00000178171 AMER3 APC membrane recruitment protein 3 0.015986308 [Source:HGNC Symbol;Acc:HGNC:26771] ENSG00000232756 0.015986308 ENSG00000130477 UNC13A unc-13 homolog A 0.016007101 [Source:HGNC Symbol;Acc:HGNC:23150] ENSG00000070886 EPHA8 EPH receptor A8 0.016008143 [Source:HGNC Symbol;Acc:HGNC:3391] ENSG00000253301 LINC01606 long intergenic non-protein coding RNA 1606 0.016008143 [Source:HGNC Symbol;Acc:HGNC:51656] ENSG00000006788 MYH13 myosin heavy chain 13 0.01606756 [Source:HGNC Symbol;Acc:HGNC:7571] ENSG00000183287 CCBE1 collagen and calcium binding EGF domains 1 0.016243979 [Source:HGNC Symbol;Acc:HGNC:29426] ENSG00000262691 0.016243979 ENSG00000125740 FOSB “FosB proto-oncogene, AP-1 transcription factore subunit 0.01663717 [Source:HGNC Symbol;Acc:HGNC:3797]” ENSG00000133083 DCLK1 doublecortin like kinase 1 0.01630694 [Source:HGNC Symbol;Acc:HGNC:2700] ENSG00000144820 ADGRG7 adhesion G protein-coupled receptor G7 0.01630694 [Source:HGNC Symbol;Acc:HGNC:19241] ENSG00000178031 ADAMTSL1 AD AMTS like 1 0.016324743 [Source:HGNC Symbol;Acc:HGNC:14632] ENSG00000187905 LRRC74B leucine rich repeat containing 74B 0.016416472 [Source:HGNC Symbol;Acc:HGNC:34301] ENSG00000221878 PSG7 pregnancy specific beta-1-glycoprotein 7 (gene/pseudogene) 0.016416472 [Source:HGNC Symbol;Acc:HGNC:9524] ENSG00000254101 LINC02055 long intergenic non-protein coding RNA 2055 0.016416472 [Source:HGNC Symbol;Acc:HGNC:52895] ENSG00000120251 GRIA2 glutamate ionotropic receptor AMPA type subunit 2 0.016488676 [Source:HGNC Symbol;Acc:HGNC:4572] ENSG00000233991 NA NA 0.016488676 ENSG00000214402 LCNL1 lipocalin like 1 0.016554945 [Source:HGNC Symbol;Acc:HGNC:34436] ENSG00000224271 0.016611527 ENSG00000257576 HSPD1P4 heat shock protein family D (Hsp60) member 1 pseudogene 4 0.016611527 [Source:HGNC Symbol;Acc:HGNC:35146] ENSG00000228549 0.016653065 ENSG00000178645 C10orf53 chromosome 10 open reading frame 53 0.016654478 [Source:HGNC Symbol;Acc:HGNC:27421] ENSG00000100078 PLA2G3 phospholipase A2 group III 0.016825197 [Source:HGNC Symbol;Acc:HGNC:17934] ENSG00000154099 DNAAF1 dynein axonemal assembly factor 1 0.016918546 [Source:HGNC Symbol;Acc:HGNC:30539] ENSG00000183242 WT1-AS WT1 antisense RNA 0.016918546 [Source:HGNC Symbol;Acc:HGNC:18135] ENSG00000124253 PCK1 phosphoenolpyruvate carboxykinase l 0.016968016 [Source:HGNC Symbol;Acc:HGNC:8724] ENSG00000183304 FAM9A family with sequence similarity 9 member A 0.016968016 [Source:HGNC Symbol;Acc:HGNC:18403] ENSG00000210127 MT-TA mitochondrially encoded tRNA alanine 0.016968016 [Source:HGNC Symbol;Acc:HGNC:7475] ENSG00000258679 0.016968016 ENSG00000130287 NCAN neurocan 0.016985672 [Source:HGNC Symbol;Acc:HGNC:2465] ENSG00000088340 FER1L4 “fer-l like family member 4, pseudogene 0.017112355 [Source:HGNC Symbol;Acc:HGNC:15801]” ENSG00000196415 PRTN3 proteinase 3 0.017180036 [Source:HGNC Symbol;Acc:HGNC:9495] ENSG00000135917 SLC19A3 solute carrier family 19 member 3 0.017339051 [Source:HGNC Symbol;Acc:HGNC:16266] ENSG00000233539 0.017342649 ENSG00000176584 DMBT1P1 deleted in malignant brain tumors 1 pseudogene 1 0.017392388 [Source:HGNC Symbol;Acc:HGNC:49497] ENSG00000135097 MSI1 musashi RNA binding protein 1 0.017394805 [Source:HGNC Symbol;Acc:HGNC:7330] ENSG00000091128 LAMB4 laminin subunit beta 4 0.017415673 [Source:HGNC Symbol;Acc:HGNC:6491] ENSG00000168367 LINC00917 long intergenic non-protein coding RNA 917 0.017415673 [Source:HGNC Symbol;Acc:HGNC:48607] ENSG00000224668 IPO8P1 importin 8 pseudogene 1 0.017704945 [Source:HGNC Symbol;Acc:HGNC:41955] ENSG00000165757 JCAD junctional cadherin 5 associated 0.017712329 [Source:HGNC Symbol;Acc:HGNC:29283] ENSG00000166558 SLC38A8 solute carrier family 38 member 8 0.017722732 [Source:HGNC Symbol;Acc:HGNC:32434] ENSG00000185467 KPNA7 karyopherin subunit alpha 7 0.017767827 [Source:HGNC Symbol;Acc:HGNC:21839] ENSG00000247699 0.017813935 ENSG00000248975 0.017824111 ENSG00000179813 FAM216B family with sequence similarity 216 member B 0.01797203 [Source:HGNC Symbol;Acc:HGNC:26883] ENSG00000188706 ZDHHC9 zince finger DHHC-type containing 9 0.018020454 [Source:HGNC Symbol;Acc:HGNC:18475] ENSG00000135472 FAIM2 Fas apoptotic inhibitory molecule 2 0.018071818 [Source:HGNC Symbol;Acc:HGNC:17067] ENSG00000173572 NLRP13 NLR family pyrin domain containing 13 0.018071818 [Source:HGNC Symbol;Acc:HGNC:22937] ENSG00000089199 CHGB chromogranin B 0.018179173 [Source:HGNC Symbol;Acc:HGNC:1930] ENSG00000188112 C6orf132 chromosome 6 open reading frame 132 0.018577564 [Source:HGNC Symbol;Acc:HGNC:21288] ENSG00000187068 C3orf70 chromosome 3 open reading frame 70 0.018587013 [Source:HGNC Symbol;Acc:HGNC:33731] ENSG00000233973 LINC01360 long intergenic non-protein coding RNA 1360 0.018588752 [Source:HGNC Symbol;Acc:HGNC:50593] ENSG00000164265 SCGB3A2 secretoglobin family 3 A member 2 0.018614288 [Source:HGNC Symbol;Acc:HGNC:18391] ENSG00000176769 TCERG1L transcription elongation regulator 1 like 0.018783363 [Source:HGNC Symbol;Acc:HGNC:23533] ENSG00000179709 NLRP8 NLR family pyrin domain containing 8 0.018812736 [Source:HGNC Symbol;Acc:HGNC:22940] ENSG00000251557 HNRNPKP3 heterogeneous nuclear ribonucleoprotein K pseudogene 3 0.018866754 [Source:HGNC Symbol;Acc:HGNC:42376] ENSG00000149654 CDH22 cadherin 22 0.018978105 [Source:HGNC Symbol;Acc:HGNC:13251] ENSG00000170426 SDR9C7 short chain dehydrogenase/reductase family 9C member 7 0.018978105 [Source:HGNC Symbol;Acc:HGNC:29958] ENSG00000225637 0.019088297 ENSG00000142408 CACNG8 calcium voltage-gated channel auziliary subunit gamma 8 0.019108077 [Source:HGNC Symbol;Acc:HGNC:13628] ENSG00000230873 STMND1 stathmin domain containing 1 0.01920241 [Source:HGNC Symbol;Acc:HGNC:44668] ENSG00000236404 VLDLR-AS1 VLDLR antisense RNA 1 0.01920241 [Source:HGNC Symbol;Acc:HGNC:49621] ENSG00000170927 PKHD1 “PKHD1, fibrocystin/polycutin 0.019345013 [Source:HGNC Symbol;Acc:HGNC:9016]” ENSG00000237289 CKMT1B “creatine kinase, mitochondrial 1B 0.019345013 [Source:HGNC Symbol;Acc:HGNC:1995]” ENSG00000229817 0.019542531 ENSG00000259176 NA NA 0.019829586 ENSG00000124092 CTCFL CCCTC-binding factor like 0.019839425 [Source:HGNC Symbol;Acc:HGNC:16234] ENSG00000259156 CHEK2P2 checkpoint kinase 2 pseudogene 2 0.019859771 [Source:HGNC Symbol;Acc:HGNC:43578] ENSG00000203805 PLPP4 phosopholipid phosphatase 4 0.019917239 [Source:HGNC Symbol;Acc:HGNC:23531] ENSG00000163914 RHO rhodopsin 0.019927103 [Source:HGNC Symbol;Acc:HGNC:10012] ENSG00000224435 NF1P6 neurofibromin 1 pseudogene 6 0.019927103 [Source:HGNC Symbol;Acc:HGNC:7771] ENSG00000240707 LINC01168 long intergenic non-protein coding RNA 1168 0.019935944 [Source:HGNC Symbol;Acc:HGNC:49537] ENSG00000130045 NXNL2 nucleoredoxin like 2 0.020063533 [Source:HGNC Symbol;Acc:HGNC:30482] ENSG00000162062 TEDC2 tubulin epsilon and delta complex 2 0.020213465 [Source:HGNC Symbol;Acc:HGNC:25849] ENSG00000172752 COL6A5 collagen type VI alpha 5 chain 0.020225168 [Source:HGNC Symbol;Acc:HGNC:26674] ENSG00000101871 MID1 midline 1 0.020247513 [Source:HGNC Symbol;Acc:HGNC:7095] ENSG00000137648 TMPRSS4 transmembrane serine protease 4 0.020387859 [Source:HGNC Symbol;Acc:HGNC:11878] ENSG00000166473 PKD1L2 polycystin 1 like 2 (gene/pseudogene) 0.020387859 [Source:HGNC Symbol;Acc:HGNC:21715] ENSG00000257907 EEF1A1P17 eukaryotic translation elongation factor 1 alpha 1 pseudogene 17 0.020486161 [Source:HGNC Symbol;Acc:HGNC:37890] ENSG00000128917 DLL4 delta like canonical Notch ligand 4 0.020505106 [Source:HGNC Symbol;Acc:HGNC:2910] ENSG00000259380 0.020626924 ENSG00000179766 ATP8B5P “ATPase phospholipid transporting 8B5, pseudogene 0.02065324 [Source:HGNC Symbol;Acc:HGNC:27245]” ENSG00000204624 DISP3 dispatched RND transporter family member 3 0.02065324 [Source:HGNC Symbol;Acc:HGNC:29251] ENSG00000163689 C3orf67 chromosome 3 open reading frame 67 0.020743462 [Source:HGNC Symbol;Acc:HGNC:24763] ENSG00000132321 IQCA1 IQ motif containing with AAA domain 1 0.020807093 [Source:HGNC Symbol;Acc:HGNC:26195] ENSG00000249119 MTND6P4 mitochondrially encoded NADH:ubiquinone 0.020807093 oxidoreductase core subunit 6 [Source:HGNC Symbol;Acc:HGNC:39467] ENSG00000019505 SYT13 synaptotagmin 13 0.020829887 [Source:HGNC Symbol;Acc:HGNC:14962] ENSG00000143469 SYT14 synaptotagmin 14 0.020885035 [Source:HGNC Symbol;Acc:HGNC:23143] ENSG00000196136 SERPINA3 serpin family A member 3 0.02099734 [Source:HGNC Symbol;Acc:HGNC:16] ENSG00000165816 VWA2 von Willebrand factor A domain containing 2 0.021329095 [Source:HGNC Symbol;Acc:HGNC:24709] ENSG00000183317 EPHA10 EPH receptor A10 0.021329095 [Source:HGNC Symbol;Acc:HGNC:19987] ENSG00000072041 SLC6A15 solute carrier family 6 member 15 0.021369466 [Source:HGNC Symbol;Acc:HGNC:13621] ENSG00000009709 PAX7 paired box 7 0.021525887 [Source:HGNC Symbol;Acc:HGNC:8621] ENSG00000172350 ABCG4 ATP binding cassette subfamily G member 4 0.021525887 [Source:HGNC Symbol;Acc:HGNC:13884] ENSG00000183876 ARSI arylsulfatase family member I 0.021711339 [Source:HGNC Symbol;Acc:HGNC:32521] ENSG00000213934 HBG1 hemoglobin subunit gamma l 0.02185053 [Source:HGNC Symbol;Acc:HGNC:4831] ENSG00000186526 CYP4F8 cytochrome P450 family 4 subfamily F member 8 0.021913633 [Source:HGNC Symbol;Acc:HGNC:2648] ENSG00000161940 BCL6B B cell CLL/lymphoma 6B 0.021959359 [Source:HGNC Symbol;Acc:HGNC:1002] ENSG00000164093 PITX2 paired like homeodomain 2 0.02227554 [Source:HGNC Symbol;Acc:HGNC:9005] ENSG00000110786 PTPN5 “protein tyrosine phosphatase, non-receptor type 5 0.022304898 [Source:HGNC Symbol;Acc:HGNC:9657]” ENSG00000145642 SHISAL2B shisa like 2B 0.022689972 [Source:HGNC Symbol;Acc:HGNC:34236] ENSG00000260411 NA NA 0.022689972 ENSG00000135409 AMHR2 anti-Mullerian hormone receptor type 2 0.022721606 [Source:HGNC Symbol;Acc:HGNC:465] ENSG00000259458 0.022776502 ENSG00000068078 FGFR3 fibroblast growth factor receptor 3 0.022896021 [Source:HGNC Symbol;Acc:HGNC:3690] ENSG00000161243 FBXO27 F-box protein 27 0.023440646 [Source:HGNC Symbol;Acc:HGNC:18753] ENSG00000101004 NINL ninein like 0.023637109 [Source:HGNC Symbol;Acc:HGNC:29163] ENSG00000121207 LRAT lecithin retinol acyltransferase 0.023637109 [Source:HGNC Symbol;Acc:HGNC:6685] ENSG00000140527 WDR93 WD repeat domain 93 0.023652058 [Source:HGNC Symbol;Acc:HGNC:26924] ENSG00000236824 BCYRN1 brain cytoplasmic RNA 1 0.023652058 [Source:HGNC Symbol;Acc:HGNC:1022] ENSG00000101203 COL20A1 collagen type XX alpha 1 chain 0.023671204 [Source:HGNC Symbol;Acc:HGNC:14670] ENSG00000233977 0.023671204 ENSG00000148408 CACNA1B calcium voltage-gated channel subunit alpha1 B 0.02389629 [Source:HGNC Symbol;Acc:HGNC:1389] ENSG00000134240 HMGCS2 3-hydroxy-3-methylglutaryl-CoA synthase 2 0.023926586 [Source:HGNC Symbol;Acc:HGNC:5008] ENSG00000112186 CAP2 cyclase associated actin cytoskeleton regulatory protein 2 0.024121501 [Source:HGNC Symbol;Acc:HGNC:20039] ENSG00000182256 GABRG3 gamma-aminobutyric acid type A receptor gamma3 subunit 0.024155164 iSource:HGNC Symbol;Acc:HGNC:4088] ENSG00000166159 LRTM2 leucine rich repeats and transmembrane domains 2 0.024214399 [Source:HGNC Symbol;Acc:HGNC:32443] ENSG00000132972 RNF17 ring finger protein 17 0.024283188 [Source:HGNC Symbol;Acc:HGNC:10060] ENSG00000156076 WIF1 WNT inhibitory factor 1 0.02423188 [Source:HGNC Symbol;Acc:HGNC:18081] ENSG00000261649 GOLGA6L7 golgin A6 family like 7 0.024421599 [Source:HGNC Symbol;Acc:HGNC:37442] ENSG00000112238 PRDM13 PR/SET domain 13 0.02443315 [Source:HGNC Symbol;Acc:HGNC:13998] ENSG00000166391 MOGAT2 monoacylglycerol O-acyltransferase 2 0.024463522 [Source:HGNC Symbol;Acc:HGNC:23248] ENSG00000166869 CHP2 calcineurin like EF-hand protein 2 0.024463522 [Source:HGNC Symbol;Acc:HGNC:24927] ENSG00000218823 PAPOLB poly(A) polymerase beta 0.024463522 [Source:HGNC Symbol;Acc:HGNC:15970] ENSG00000265041 0.024463522 ENSG00000133124 IRS4 insulin receptor substrate 4 0.024526611 [Source:HGNC Symbol;Acc:HGNC:6128] ENSG00000118733 OLFM3 olfactomedin 3 0.024577949 [Source:HGNC Symbol;Acc:HGNC:17990] ENSG00000196091 MYBPC1 “myosin binding protein C, slow type 0.024577949 [Source:HGNC Symbol;Acc:HGNC:7549]” ENSG00000105357 MYH14 myosin heavy chain 14 0.025148395 [Source:HGNC Symbol;Acc:HGNC:23212] ENSG00000167757 KLK11 kallikrein related peptidase 11 0.025148395 [Source:HGNC Symbol;Acc:HGNC:6359] ENSG00000226068 HNRNPA3P4 heterogeneous nuclear ribonucleoprotein A3 pseudogene 4 0.025148395 [Source:HGNC Symbol;Acc:HGNC:39773] ENSG00000260072 0.025148395 ENSG00000130226 DPP6 dipeptidyl peptidase like 6 0.02515224 [Source:HGNC Symbol;Acc:HGNC:3010] ENSG00000144648 ACKR2 atypical chemokine receptor 2 0.02527518 [Source:HGNC Symbol;Acc:HGNC:1565] ENSG00000169862 CTNND2 catenin delta 2 0.025318552 [Source:HGNC Symbol;Acc:HGNC:2516] ENSG00000137766 UNC13C unc-13 homolog C 0.025345898 [Source:HGNC Symbol;Acc:HGNC:23149] ENSG00000261177 0.025565995 ENSG00000060656 PTPRU “protein tryosine phosphatase, receptor type U 0.025652607 [Source:HGNC Symbol;Acc:HGNC:9683]” ENSG00000260305 NTRK3-AS1 NTRK3 antisense RNA 1 0.02580767 [Source:HGNC Symbol;Acc:HGNC:27532] ENSG00000187955 COL14A1 collagen type XIV alpha 1 chain 0.025820696 [Source:HGNC Symbol;Acc:HGNC:2191] ENSG00000089225 TBX5 T-box 5 0.025834296 [Source:HGNC Symbol;Acc:HGNC:11604] ENSG00000224209 LINC00466 long intergenic non-protein coding RNA 466 0.025987072 [Source:HGNC Symbol;Acc:HGNC:27294] ENSG00000151474 FRMD4A FERM domain containing 4A 0.026041989 [Source:HGNC Symbol;Acc:HGNC:25491] ENSG00000039987 BEST2 bestrophin 2 0.026152714 [Source:HGNC Symbol;Acc:HGNC:17107] ENSG00000266795 NA NA 0.026198035 ENSG00000181143 MUC16 “mucin 16, cell surface associated 0.026247081 [Source:HGNC Symbol;Acc:HGNC:15582]” ENSG00000069431 ABCC9 ATP binind cassette subfamily C member 9 0.026486685 [Source:HGNC Symbol;Acc:HGNC:60] ENSG00000100312 ACR acrosin 0.02666392 [Source:HGNC Symbol;Acc:HGNC:126] ENSG00000254042 0.026721536 ENSG00000180251 SLC9A4 solute carrier family 9 member A4 [Source:HGNC Symbol;Acc:HGNC:11077] 0.026759131 ENSG00000237390 ENSG00000246695 RASSF8-AS1 RASSF8 antisense RNA 1 0.026759131 [Source:HGNC Symbol;Acc:HGNC:48637] ENSG00000256612 CYP2B7P “cytochroma P450 family 2 subfamily B member 7, pseudogene 0.026759131 [Source:HGNC Symbol;Acc:HGNC:2616]” ENSG00000165973 NELL1 neural EGFL like 1 0.026774963 [Source:HGNC Symbol;Acc:HGNC:7750] ENSG00000172900 0.02698221 ENSG00000149926 FAM57B family with sequence similarity 57 member B 0.02707614 [Source:HGNC Symbol;Acc:HGNC:25295] ENSG00000107295 SH3GL2 “SH3 domain containing GRB2 like 2, endophilin A1 0.027164347 [Source:HGNC Symbol;Acc:HGNC:10831]” ENSG00000173227 SYT12 synaptotagmin 12 0.027164347 [Source:HGNC Symbol;Acc:HGNC:18381] ENSG00000173013 CCDC96 coiled-coil domain containing 96 0.027208218 [Source:HGNC Symbol;Acc:HGNC:26900] ENSG00000268460 0.02723306 ENSG00000234512 TLR12P “toll like receptor 12, pseudogene 0.027406947 [Source:HGNC Symbol;Acc:HGNC:31754]” ENSG00000135931 ARMC9 armadillo repeat containing 9 0.02759323 [Source:HGNC Symbol;Acc:HGNC:20730] ENSG00000148702 HABP2 hyaluronan binding protien 2 0.027601758 [Source:HGNC Symbol;Acc:HGNC:4798] ENSG00000136535 TBR1 “T-box, brain 1 0.028071412 [Source:HGNC Symbol;Acc:HGNC:11590]” ENSG00000122121 XPNPEP2 X-prolyl aminopeptidase 2 0.028133383 [Source:HGNC Symbol;Acc:HGNC:12823] ENSG00000170442 KRT86 keratin 86 0.028133383 [Source:HGNC Symbol;Acc:HGNC:6463] ENSG00000197408 CYP2B6 cytochrome P450 family 2 subfamily B member 6 0.028133383 [Source:HGNC Symbol;Acc:HGNC:2615] ENSG00000107807 TLX1 T cell leukemia homeobox 1 0.028207054 [Source:HGNC Symbol;Acc:HGNC:5056] ENSG00000164694 FNDC1 fibronectin type III domain containing 1 0.028207054 [Source:HGNC Symbol;Acc:HGNC:21184] ENSG00000185313 SCN10A sodium voltage-gated channel alpha subunit 10 0.028207054 [Source:HGNC Symbol;Acc:HGNC:10582] ENSG00000164107 HAND2 heart and neural crest derivatives expressed 2 0.028335907 [Source:HGNC Symbol;Acc:HGNC:4808] ENSG00000133454 MYO18B myosin XVIIIB 0.028417113 [Source:HGNC Symbol;Acc:HGNC:18150] ENSG00000167723 TRPV3 transient receptor potential cation channel subfamily V member 3 0.028422765 [Source:HGNC Symbol;Acc:HGNC:18084] ENSG00000184012 TMPRSS2 transmembrane serine protease 2 0.028422765 [Source:HGNC Symbol;Acc:HGNC:11876] ENSG00000233485 0.028645846 ENSG00000261466 0.028645846 ENSG00000119547 ONECUT2 one cut homeobox 2 0.028669408 [Source:HGNC Symbol;Acc:HGNC:8139] ENSG00000237222 LINC01968 long intergenic non-protein coding RNA 1968 0.028800664 [Source:HGNC Symbol;Acc:HGNC:52794] ENSG00000137573 SULF1 sulfatase 1 0.028919683 [Source:HGNC Symbol;Acc:HGNC:20391] ENSG00000161609 CCDC155 coiled-coil domain containing 155 0.028967146 [Source:HGNC Symbol;Acc:HGNC:26520] ENSG00000250546 0.028987628 ENSG00000226057 PHF2P2 PHD finger protein 2 pseudogene 2 0.029139308 [Source:HGNC Symbol;Acc:HGNC:38808] ENSG00000177045 SIX5 SIX homeobox 5 0.029298722 [Source:HGNC Symbol;Acc:HGNC:10891] ENSG00000124440 HIF3A hypoxia inducible factor 3 alpha subunit 0.029322985 [Source:HGNC Symbol;Acc:HGNC:15825] ENSG00000234828 IQCM IQ motif containing M 0.029461236 [Source:HGNC Symbol;Acc:HGNC:53443] ENSG00000116721 PRAMEF1 PRAME family member 1 0.029473652 [Source:HGNC Symbol;Acc:HGNC:28840] ENSG00000238116 0.029473652 ENSG00000106689 LHX2 LIM homeobox 2 0.029512187 [Source:HGNC Symbol;Acc:HGNC:6594] ENSG00000169344 UMOD uromodulin 0.02959944 [Source:HGNC Symbol;Acc:HGNC:12559] ENSG00000174279 EVX2 even-skipped homeobox 2 0.029661965 [Source:HGNC Symbol;Acc:HGNC:3507] ENSG00000128573 FOXP2 forkhead box P2 0.029779428 [Source:HGNC Symbol;Acc:HGNC:13875] ENSG00000251596 HADHAP1 “hydroxyacyl-CoA dehydrogenase/3-ketoacyl-CoA 0.029954508 thiolase/enoyl-CoA hydratase (trifunctional protein), alpha subunit pseudogene 1 [Source:HGNC Symbol;Acc:HGNC:4802]” ENSG00000002746 HECW1 “HECT, C2 and WW domain containing E3 0.029980732 ubiquitin protein ligase 1 [Source:HGNC Symbol;Acc:HGNC:22195]” ENSG00000081248 CACNA1S calcium voltage-gated channel subunit alpha1 S 0.029997906 [Source:HGNC Symbol;Acc:HGNC:1397] ENSG00000166596 CFAP52 cilia and flagella associated protein 52 0.030027148 [Source:HGNC Symbol;Acc:HGNC:16053] ENSG00000205176 REXO1L1P “REXO1 like 1, pseudogene 0.030066221 [Source:HGNC Symbol;Acc:HGNC:24660]” ENSG00000152910 CNTNAP4 contactin associated protein like 4 0.030144659 [Source:HGNC Symbol;Acc:HGNC:18747] ENSG00000106078 COBL cordon-bleu WH2 repeat protein 0.030263618 [Source:HGNC Symbol;Acc:HGNC:22199] ENSG00000177103 DSCAML1 DS cell adhesion molecule like 1 0.030299369 [Source:HGNC Symbol;Acc:HGNC:14656] ENSG00000131044 TTLL9 tubulin tyrosine ligase like 9 0.030317293 [Source:HGNC Symbol;Acc:HGNC:16118] ENSG00000170703 TTLL6 tubulin tyrosine ligase like 9 0.030472844 [Source:HGNC Symbol;Acc:HGNC:26664] ENSG00000165379 LRFN5 leucine rich repeat and fibronectin type III domain containing 5 0.030532839 [Source:HGNC Symbol;Acc:HGNC:20360] ENSG00000198929 NOS1AP nitric oxide synthase 1 adaptor protein 0.030532839 [Source:HGNC Symbol;Acc:HGNC:16859] ENSG00000236253 SLC25A3P1 solute carrier family 25 member 3 pseuodogene 1 0.030574302 [Source:HGNC Symbol;Acc:HGNC:26869] ENSG00000205667 ARSH arylsulfatase family member H 0.030639161 [Source:HGNC Symbol;Acc:HGNC:32488] ENSG00000226440 0.030639161 ENSG00000131183 SLC34A1 solute carrier family 34 member 1 0.030803937 [Source:HGNC Symbol;Acc:HGNC:11019] ENSG00000225649 0.030847037 ENSG00000006283 CACNA1G calcium voltage-gated channel subunit alpha1 G 0.030936635 [Source:HGNC Symbol;Acc:HGNC:1394] ENSG00000230392 0.030977697 ENSG00000234130 0.031067495 ENSG00000095637 SORBS1 sorbin and SH3 domain containing 1 0.031086939 [Source:HGNC Symbol;Acc:HGNC:14565] ENSG00000198010 DLGAP2 DLG associated protein 2 0.031235492 [Source:HGNC Symbol;Acc:HGNC:2906] ENSG00000102290 PCDH11X protocadherin 11 X-linked 0.031415941 [Source:HGNC Symbol;Acc:HGNC:8656] ENSG00000260027 HOXB7 homeobox B7 0.031452441 [Source:HGNC Symbol;Acc:HGNC:5118] ENSG00000105664 COMP cartilage oligomeric matrix protein 0.03516506 [Source:HGNC Symbol;Acc:HGNC:2227] ENSG00000006071 ABCC8 ATP binding cassette subfamily C member 8 0.031578145 [Source:HGNC Symbol;Acc:HGNC:59] ENSG00000077522 ACTN2 actinin alpha 2 0.031657927 [Source:HGNC Symbol;Acc:HGNC:164] ENSG00000248966 BCLAF1P1 BCL2 associated transcription factor 1 pseudogene 1 0.031733491 [Source:HGNC Symbol;Acc:HGNC:51329] ENSG00000124749 COL21A1 collagen type XXI alpha 1 chain 0.031814031 [Source:HGNC Symbol;Acc:HGNC:17025] ENSG00000142675 CNKSR1 connector enhancer of kinase suppressor of Ras 1 0.031815396 [Source:HGNC Symbol;Acc:HGNC:19700] ENSG00000116748 AMPD1 adenosin monophosphate deaminase 1 0.031850457 [Source:HGNC Symbol;Acc:HGNC:468] ENSG00000181355 OFCC1 orofacial cleft 1 candiate 1 0.03221007 [Source:HGNC Symbol;Acc:HGNC:21017] ENSG00000162510 MATN1 “matrilin 1, cartilage matrix protein 0.032424937 [Source:HGNC Symbol;Acc:HGNC:6907]” ENSG00000232392 0.032424937 ENSG00000123572 NRK Nik related kinase 0.032537919 [Source:HGNC Symbol;Acc:HGNC:25391] ENSG00000267324 0.032537919 ENSG00000196361 ELAVL3 ELAV like RNA binding protein 3 0.032579843 [Source:HGNC Symbol;Acc:HGNC:3314] ENSG00000204661 C5orf60 chromosome 5 open reading fram 60 0.032697662 [Source:HGNC Symbol;Acc:HGNC:27753] ENSG00000224059 HSPA8P16 heat shock protein family A (Hsp70) member 8 pseudogene 16 0.03275969 [Source:HGNC Symbol;Acc:HGNC:44931] ENSG00000114019 AMOTL2 angiomotin like 2 0.033101928 [Source:HGNC Symbol;Acc:HGNC:17812] ENSG00000134871 COL4A2 collagen type IV alpha 2 chain 0.033101928 [Source:HGNC Symbol;Acc:HGNC:2203] ENSG00000162706 CADM3 cell adhesion molecule 3 0.033101928 [Source:HGNC Symbol;Acc:HGNC:17601] ENSG00000188782 CATSPER4 cation channel sperm associated 4 0.033196706 [Source:HGNC Symbol;Acc:HGNC:23220] ENSG00000147689 FAM83A family with sequence similarity 83 member A 0.033349502 [Source:HGNC Symbol;Acc:HGNC:28210] ENSG00000079841 RIMS1 regulating synaptic membrane exocytosis 1 0.033394348 [Source:HGNC Symbol;Acc:HGNC:17282] ENSG00000103647 CORO2B coronin 2B 0.033419797 [Source:HGNC Symbol;Acc:HGNC:2256] ENSG00000112499 SLC22A2 solute carrier family 22 member 2 0.033434322 [Source:HGNC Symbol;Acc:HGNC:10966] ENSG00000183856 IQGAP3 IQ motif containing GTPase activating protein 3 0.033434322 [Source:HGNC Symbol;Acc:HGNC:20669] ENSG00000165300 SLITRK5 SLIT and NTRK like family member 5 0.033483825 [Source:HGNC Symbol;Acc:HGNC:20295] ENSG00000229972 IQCF3 IQ motif containing F3 0.033483825 [Source:HGNC Symbol;Acc:HGNC:31816] ENSG00000261949 GFY golgi associated olfactory signaling regulator 0.033483825 [Source:HGNC Symbol;Acc:HGNC:44663] ENSG00000171487 NLRP5 NLR family pyrin domain containing 5 0.033631095 [Source:HGNC Symbol;Acc:HGNC:21269] ENSG00000129946 SHC2 SHC adaptor protein 2 0.033699292 [Source:HGNC Symbol;Acc:HGNC:29869] ENSG00000117501 MROH9 maestro heat like repeat family member 9 0.03391477 [Source:HGNC Symbol;Acc:HGNC:26287] ENSG00000136574 GATA4 GATA binding protein 4 0.034539616 [Source:HGNC Symbol;Acc:HGNC:4173] ENSG00000106648 GALNTL5 polypeptide N-acetylgalactosaminyltransferase like 5 0.034620414 [Source:HGNC Symbol;Acc:HGNC:21725] ENSG00000188086 PRSS45 serine protease 45 0.034840251 [Source:HGNC Symbol;Acc:HGNC:30717] ENSG00000234537 0.034858474 ENSG00000226741 LINC02554 long intergenic non-protein coding RNA 2554 0.034969314 [Source:HGNC Symbol;Acc:HGNC:53594] ENSG00000004948 CALCR calcitonin receptor 0.034980702 [Source:HGNC Symbol;Acc:HGNC:1440] ENSG00000142549 IGLON5 IgLON family member 5 0.034980702 [Source:HGNC Symbol;Acc:HGNC:34550] ENSG00000250519 0.034980702 ENSG00000183908 LRRC55 leucine rich repeat containing 55 0.035005257 [Source:HGNC Symbol;Acc:HGNC:32324] ENSG00000253974 NRG1-IT1 NRG1 intronic transcript 1 0.035154264 [Source:HGNC Symbol;Acc:HGNC:43633] ENSG00000162738 VANGL2 VANGL planar cell polarity protein 2 0.035338561 [Source:HGNC Symbol;Acc:HGNC:15511] ENSG00000115648 MLPH melanophilin 0.03575577 [Source:HGNC Symbol;Acc:HGNC:29643] ENSG00000187997 C17orf99 chromosome 17 open reading fram 99 0.03575577 [Source:HGNC Symbol;Acc:HGNC:34490] ENSG00000140279 DUOX2 dual oxidase 2 0.035790036 [Source:HGNC Symbol;Acc:HGNC:13273] ENSG00000168077 SCARA3 scavenger receptor class A member 3 0.035804565 [Source:HGNC Symbol;Acc:HGNC:19000] ENSG00000159337 PLA2G4D phosopholipase A2 group IVD 0.035823277 [Source:HGNC Symbol;Acc:HGNC:30038] ENSG00000183580 FBXL7 F-box and leucine rich repeat protein 7 0.035823277 [Source:HGNC Symbol;Acc:HGNC:13604] ENSG00000218586 0.035823277 ENSG00000184809 B3GALT5-AS1 B3GALT5 antisense RNA 1 0.035845893 [Source:HGNC Symbol;Acc:HGNC:16424] ENSG00000132975 GPR12 G protein-coupled receptor 12 0.035938935 [Source:HGNC Symbol;Acc:HGNC:4466] ENSG00000142910 TINAGL1 tubulointerstitial nephritis antigen like 1 0.035938935 [Source:HGNC Symbol;Acc:HGNC:19168] ENSG00000075891 PAX2 paired box 2 0.035996581 [Source:HGNC Symbol;Acc:HGNC:8616] ENSG00000186393 KRT26 keratin 26 0.036025366 [Source:HGNC Symbol;Acc:HGNC:30840] ENSG00000167779 IGFBP6 insulin like growth factor binding protein 6 0.036065767 [Source:HGNC Symbol;Acc:HGNC:5475] ENSG00000232667 0.036065767 ENSG00000263711 0.036105875 ENSG00000205054 LINC01121 long intergenic non-protein coding RNA 1121 0.036105875 [Source:HGNC Symbol;Acc:HGNC:49266] ENSG00000146950 SHROOM2 shroom family member 2 0.036340531 [Source:HGNC Symbol;Acc:HGNC:630] ENSG00000143867 OSR1 odd-skipped related transciption factor 1 0.036393162 [Source:HGNC Symbol;Acc:HGNC:8111] ENSG00000205976 0.036631586 ENSG00000196862 RGPD4 RANBP2-like and GRIP domain containing 4 0.034154755 [Source:HGNC Symbol;Acc:HGNC:32417] ENSG00000148513 ANKRD30A ankyrin repeat domain 30A 0.037278195 [Source:HGNC Symbol;Acc:HGNC:17234] ENSG00000101057 MYBL2 MYB proto-oncogene like 2 0.037361359 [Source:HGNC Symbol;Acc:HGNC:7548] ENSG00000139144 PIK3C2G phosphatidylinositol-4-phosphate 3-kinase catalytic subunit type 2 0.037546969 [Source:HGNC Symbol;Acc:HGNC:8973] ENSG00000247213 LINC01498 long intergenic non-protein coding RNA 1498 0.037546969 [Source:HGNC Symbol;Acc:HGNC:51164] ENSG00000145242 EPHA5 EPH recpetor A5 0.037630556 [Source:HGNC Symbol;Acc:HGNC:3389] ENSG00000249215 NCOA4P4 nuclear receptor coactivator 4 pseudogene 4 0.037740576 [Source:HGNC Symbol;Acc:HGNC:52405] ENSG00000079112 CDH17 cadherin 17 0.037745905 [Source:HGNC Symbol;Acc:HGNC:1756] ENSG00000166118 SPATA19 spermatogenesis associated 19 0.037802718 [Source:HGNC Symbol;Acc:HGNC:30614] ENSG00000162006 MSLNL mesothelin-like 0.037970738 [Source:HGNC Symbol;Acc:HGNC:14170] ENSG00000187123 LYPD6 LY6/PLAUR domain containing 6 0.037980544 [Source:HGNC Symbol;Acc:HGNC:28751] ENSG00000104313 EYA1 EYA transcriptional coactivator and phosphatase 1 0.038059131 [Source:HGNC Symbol;Acc:HGNC:3519] ENSG00000237250 0.038171217 ENSG00000105290 APLP1 amyloid beta precursor like protein 1 0.038576481 [Source:HGNC Symbol;Acc:HGNC:597] ENSG00000138650 PCDH10 protocadherin 10 0.038631087 [Source:HGNC Symbol;Acc:HGNC:13404] ENSG00000198914 POU3F3 POU class 3 homeobox 3 0.03865691 [Source:HGNC Symbol;Acc:HGNC:9216] ENSG00000117114 ADGRL2 adhesion G protein-coupled receptor L2 0.039101789 [Source:HGNC Symbol;Acc:HGNC:18582] ENSG00000185737 NRG3 neuregulin 3 0.039101789 [Source:HGNC Symbol;Acc:HGNC:7999] ENSG00000197085 NPSR1-AS1 NPSR1 antisense RNA 1 0.039361047 [Source:HGNC Symbol;Acc:HGNC:22128] ENSG00000230102 LINC02028 long intergenic non-protein coding RNA 2028 0.039602594 [Source:HGNC Symbol;Acc:HGNC:27718] ENSG00000241158 ADAMTS9-AS1 ADAMTS9 antisense RNA 1 0.039646513 [Source:HGNC Symbol;Acc:HGNC:40625] ENSG00000146005 PSD2 pleckstrin and Sec7 domain containing 2 0.039852243 [Source:HGNC Symbol;Acc:HGNC:19092] ENSG00000171533 MAP6 microtubule associated protein 6 0.040171006 [Source:HGNC Symbol;Acc:HGNC:6868] ENSG00000164294 GPX8 glutathione perozidase 8 (putative) 0.040207131 [Source:HGNC Symbol;Acc:HGNC:33100] ENSG00000054356 PTPRN “protein tyrosine phosphatase, receptor type N 0.040248543 [Source:HGNC Symbol;Acc:HGNC:9676]” ENSG00000077080 ACTL6B actin like 6B 0.040248543 [Source:HGNC Symbol;Acc:HGNC:160] ENSG00000141434 MEP1B meprin A subunit beta 0.040590193 [Source:HGNC Symbol;Acc:HGNC:7020] ENSG00000183067 IGSF5 immunoglobulin superfamily member 5 0.040590193 [Source:HGNC Symbol;Acc:HGNC:5952] ENSG00000112337 SLC17A2 solute carrier family 17 member 2 0.040803316 [Source:HGNC Symbol;Acc:HGNC:10930] ENSG00000161682 FAM171A2 family with sequence similarity 171 member A2 0.040923418 [Source:HGNC Symbol;Acc:HGNC:30480] ENSG00000116833 NR5A2 nuclear receptor subfamily 5 group A member 2 0.040938395 [Source:HGNC Symbol;Acc:HGNC:7984] ENSG00000143355 LHX9 LIM homeobox 9 0.041155655 [Source:HGNC Symbol;Acc:HGNC:14222] ENSG00000139767 SRRM4 serine/arginine repetitive matrix 4 0.041207854 [Source:HGNC Symbol;Acc:HGNC:29389] ENSG00000227036 LINC00511 long intergenic non-protein coding RNA 511 0.041207854 [Source:HGNC Symbol;Acc:HGNC:43564] ENSG00000105549 THEG theg spermatid protein 0.041581527 [Source:HGNC Symbol;Acc:HGNC:13706] ENSG00000104967 NOVA2 NOVA alternative splicing regulator 2 0.041600384 [Source:HGNC Symbol;Acc:HGNC:7887] ENSG00000183206 POTEC POTE ankyrin domain family member C 0.041620804 [Source:HGNC Symbol;Acc:HGNC:33894] ENSG00000184302 SIX6 SIX homeobox 6 0.041631474 [Source:HGNC Symbol;Acc:HGNC:10892] ENSG00000245651 0.041631474 ENSG00000179178 TMEM125 transmembrane protein 125 0.041791867 [Source:HGNC Symbol;Acc:HGNC:28275] ENSG00000231422 LINC01516 long intergenic non-protein coding RNA 1516 0.041868067 [Source:HGNC Symbol;Acc:HGNC:51211] ENSG00000104435 STMN2 stathmin 2 0.041944166 [Source:HGNC Symbol;Acc:HGNC:10577] ENSG00000185069 KRT76 keratin 76 0.042071807 [Source:HGNC Symbol;Acc:HGNC:24430] ENSG00000060709 RIMBP2 RIMS binding protein 2 0.042101327 [Source:HGNC Symbol;Acc:HGNC:30339] ENSG00000261115 TMEM178B transmembrane protein 178B 0.042193233 [Source:HGNC Symbol;Acc:HGNC:44112] ENSG00000261623 LINC02179 long intergenic non-protein coding RNA 2179 0.042224694 [Source:HGNC Symbol;Acc:HGNC:53041] ENSG00000153165 RGPD3 RANBP2-like and GRIP domain containing 3 0.042347063 [Source:HGNC Symbol;Acc:HGNC:32416] ENSG00000253230 LINC00599 long intergenic non-protein coding RNA 599 0.042450091 [Source:HGNC Symbol;Acc:HGNC:27231] ENSG00000236078 LINC01447 long intergenic non-protein coding RNA 1447 0.042463159 [Source:HGNC Symbol;Acc:HGNC:50783] ENSG00000230133 LINC01721 long intergenic non-protein coding RNA 1721 0.042512831 [Source:HGNC Symbol;Acc:HGNC:52508] ENSG00000237636 ANKRD26P3 ankyrin repeat domain 26 pseudogene 3 0.042582368 [Source:HGNC Symbol;Acc:HGNC:39689] ENSG00000264954 PRR29-AS1 PRR29 antisense RNA 1 0.042699245 [Source:HGNC Symbol;Acc:HGNC:51822] ENSG00000166689 PLEKHA7 pleckstrin homology domain containing A7 0.04272194 [Source:HGNC Symbol;Acc:HGNC:27049] ENSG00000173826 KCNH6 potassium voltage-gated channel subfamily H member 6 0.042801591 [Source:HGNC Symbol;Acc:HGNC:18862] ENSG00000253864 NA NA 0.042900836 ENSG00000166292 TMEM100 transmembrane protein 100 0.043052047 [Source:HGNC Symbol;Acc:HGNC:25607] ENSG00000137203 TFAP2A transcription factor AP-2 alpha 0.043105155 [Source:HGNC Symbol;Acc:HGNC:11742] ENSG00000165970 SLC6A5 solute carrier family 6 member 5 0.043105155 [Source:HGNC Symbol;Acc:HGNC:11051] ENSG00000184908 CLCNKB chloride voltage-gated channel Kb 0.043516345 [Source:HGNC Symbol;Acc:HGNC:2027] ENSG00000197893 NRAP nebulin related anchoring protein 0.04356721 [Source:HGNC Symbol;Acc:HGNC:7988] ENSG00000169126 ARMC4 armadillo repeat containing 4 0.04363247 [Source:HGNC Symbol;Acc:HGNC:25583] ENSG00000245248 USP2-AS1 USP2 antisense RNA 1 (head to head) 0.043635087 [Source:HGNC Symbol;Acc:HGNC:48673] ENSG00000242866 STRC stereocilin 0.043658722 [Source:HGNC Symbol;Acc:HGNC:16035] ENSG00000164393 ADGRF2 adhesion G protein-coupled receptor F2 0.044026611 [Source:HGNC Symbol;Acc:HGNC:18991] ENSG00000100033 PRODH proline dehydrogenase 1 0.044045719 [Source:HGNC Symbol;Acc:HGNC:9453] ENSG00000136352 NKX2-1 NK2 homeobox 1 0.044046233 [Source:HGNC Symbol;Acc:HGNC:11825] ENSG00000165566 AMER2 APC membrane recruitment protein 2 0.044155809 [Source:HGNC Symbol;Acc:HGNC:26360] ENSG00000163995 ABLIM2 actin binding LIM protein family member 2 0.044231879 [Source:HGNC Symbol;Acc:HGNC:19195] ENSG00000165495 PKNOX2 PBX/knotted 1 homeobox 2 0.044261202 [Source:HGNC Symbol;Acc:HGNC:16714] ENSG00000144115 THNSL2 threonine synthase like 2 0.044590058 [Source:HGNC Symbol;Acc:HGNC:25602] ENSG00000157214 STEAP2 STEAP2 metalloreductase 0.044717969 [Source:HGNC Symbol;Acc:HGNC:17885] ENSG00000229240 LINC00710 long intergenic non-protein coding RNA 710 0.044849493 [Source:HGNC Symbol;Acc:HGNC:27386] ENSG00000168356 SCN11A sodium voltage-gated channel alpha subunit 11 0.044881812 [Source:HGNC Symbol;Acc:HGNC:10583] ENSG00000130508 PXDN peroxidasin 0.044899327 [Source:HGNC Symbol;Acc:HGNC:14966] ENSG00000166444 ST5 suppression of tumorigenicity 5 0.044899327 [Source:HGNC Symbol;Acc:HGNC:11350] ENSG00000140600 SH3GL3 “SH3 domain containing GRB2 like 3, endophilin A3 0.045237232 [Source:HGNC Symbol;Acc:HGNC:10832]” ENSG00000214181 NA NA 0.045237232 ENSG00000144681 STAC SH3 and cysteine rich domain 0.045389235 [Source:HGNC Symbol;Acc:HGNC:11353] ENSG00000166863 TAC3 tachykinin 3 0.045474144 [Source:HGNC Symbol;Acc:HGNC:11521] ENSG00000169436 COL22A1 collagen type XXII alpha 1 chain 0.045474144 [Source:HGNC Symbol;Acc:HGNC:22989] ENSG00000172137 CALB2 calbindin 2 0.045474144 [Source:HGNC Symbol;Acc:HGNC:1435] ENSG00000223566 TNRC18P2 trinucleotide repeat containing 18 pseudogene 2 0.045474144 [Source:HGNC Symbol;Acc:HGNC:34014] ENSG00000175267 VWA3A von Willebrand factor A domain containing 3A 0.045495146 [Source:HGNC Symbol;Acc:HGNC:27088] ENSG00000175267 VWA3A von Willebrand factor A domain containing 3A 0.045495146 [Source:HGNC Symbol;Acc:HGNC:27088] ENSG00000183780 SLC35F3 solute carrier family 35 member F3 0.045495146 [Source:HGNC Symbol;Acc:HGNC:23616] ENSG00000228983 SLC47A1P1 solute carrier family 47 member 1 pseudogene 1 0.045495146 [Source:HGNC Symbol;Acc:HGNC:51849] ENSG00000269332 GOLGA2P9 golgin A2 pseudogene 9 0.045495146 [Source:HGNC Symbol;Acc:HGNC:49921] ENSG00000081800 SLC13A1 solute carrier family 13 member 1 0.045528908 [Source:HGNC Symbol;Acc:HGNC:10916] ENSG00000155816 FMN2 formin 2 0.045228908 [Source:HGNC Symbol;Acc:HGNC:14074] ENSG00000091137 SLC26A4 solute carrier family 26 member 4 0.045601783 [Source:HGNC Symbol;Acc:HGNC:8818] ENSG00000129990 SYT5 synaptotagmin 5 0.045601783 [Source:HGNC Symbol;Acc:HGNC:11513] ENSG00000173702 MUC13 “mucin 13, cell surface associated 0.045601783 [Source:HGNC Symbol;Acc:HGNC:7511]” ENSG00000116176 TPSG1 tryptase gamma 1 0.045645845 [Source:HGNC Symbol;Acc:HGNC:14134] ENSG00000250420 AACSP1 acetoacetyl-CoA synthetase pseudogene 1 0.045645845 [Source:HGNC Symbol;Acc:HGNC:18226] ENSG00000104055 TGM5 transglutaminase 5 0.045691236 [Source:HGNC Symbol;Acc:HGNC:11781] ENSG00000109101 FOXN1 forkhead box NI 0.045781 [Source:HGNC Symbol;Acc:HGNC:12765] ENSG00000131386 GALNT15 polypeptide N-acetylgalactosaminyltransferase 15 0.045798489 [Source:HGNC Symbol;Acc:HGNC:21531] ENSG00000183016 NA NA 0.045937358 ENSG00000248746 ACTN3 actinin alpha 3 (gene/pseudogene) 0.045937358 [Source:HGNC Symbol;Acc:HGNC:165] ENSG00000259010 0.04595318 ENSG00000156687 UNC5D unc-5 netrin receptor D 0.046099925 [Source:HGNC Symbol;Acc:HGNC:18634] ENSG00000213864 EEF1B2P2 eukaryotic translation elongation factor 1 beta 2 pseudogene 2 0.046129239 [Source:HGNC Symbol;Acc:HGNC:3209] ENSG00000143107 FNDC7 fibronectin type III domain containing 7 0.046229298 [Source:HGNC Symbol;Acc:HGNC:26668] ENSG00000230615 0.046269835 ENSG00000184227 ACOT1 acyl-CoA thioesterase 1 0.046363122 [Source:HGNC Symbol;Acc:HGNC:33128] ENSG00000118194 TNNT2 “troponin T2, cardiac type 0.046453265 [Source:HGNC Symbol;Acc:HGNC:11949]” ENSG00000172995 ARPP21 cAMP regulated phosphoprotein 21 0.046453265 [Source:HGNC Symbol;Acc:HGNC:16968] ENSG00000156103 MMP16 matrix metallopeptidase 16 0.04649564 [Source:HGNC Symbol;Acc:HGNC:7162] ENSG00000164904 ALDH7A1 aldehyde dehydrogenase 7 family member A1 0.04649564 [Source:HGNC Symbol;Acc:HGNC:877] ENSG00000224743 TEX26-AS1 TEX26 antisense RNA 1 0.04649564 [Source:HGNC Symbol;Acc:HGNC:42784] ENSG00000185823 NPAP1 nuclear pore associated protein 1 0.04652545 [Source:HGNC Symbol;Acc:HGNC:1190] ENSG00000018607 ZNF806 zinc finger protein 806 0.046600673 [Source:HGNC Symbol;Acc:HGNC:33228] ENSG00000179270 C2orf71 chromosome 2 open reading frame 71 0.046600673 [Source:HGNC Symbol;Acc:HGNC:34383] ENSG00000186862 PDZD7 PDZ domain containing 7 0.04610668 [Source:HGNC Symbol;Acc:HGNC:26257] ENSG00000227525 RPL7P6 ribosomal protein L7 pseudogene 6 0.046989116 [Source:HGNC Symbol;Acc:HGNC:32430] ENSG00000236229 VEZF1P1 vascular endothelial zinc finger 1 pseudogene 1 0.047105132 [Source:HGNC Symbol;Acc:HGNC:32320] ENSG00000171564 FGB fibrinogen beta chain 0.047251427 [Source:HGNC Symbol;Acc:HGNC:3662] ENSG00000257175 0.047316621 ENSG00000248713 LOC285556 “Homo sapiens uncharacterized mRNA. 0.047420932 [Source:RefSeqmRNA;Acc:NM_001354435]” ENSG00000102287 GABRE gamma-aminobutyric acid type A receptor epsilon subunit 0.047603565 [Source:HGNC Symbol;Acc:HGNC:4085] ENSG00000150086 NA NA 0.0476766 ENSG00000168959 GRM5 glutamate metabotropic receptor 5 0.0476766 [Source:HGNC Symbol;Acc:HGNC:4597] ENSG00000184304 PRKD1 protein kinase D1 0.0476766 [Source:HGNC Symbol;Acc:HGNC:9407] ENSG00000204055 0.047795615 ENSG00000164122 ASB5 ankyrin repeat and SOCS box containing 5 0.047913021 [Source:HGNC Symbol;Acc:HGNC:17180] ENSG00000123977 DAW1 dynein assembly factor with WD repeats 1 0.047973 [Source:HGNC Symbol;Acc:HGNC:26383] ENSG00000156413 FUT6 fucosyltransferase 6 0.047988989 [Source:HGNC Symbol;Acc:HGNC:4017] ENSG00000101276 SLC52A3 solute carrier family 52 member 3 0.048129781 [Source:HGNC Symbol;Acc:HGNC:16187] ENSG00000168079 SCARA5 scavenger receptor class A member 5 0.048129781 [Source:HGNC Symbol;Acc:HGNC:28701] ENSG00000254561 0.048129781 ENSG00000223949 ROR1-AS1 ROR1 antisense RNA 1 0.04819425 [Source:HGNC Symbol;Acc:HGNC:40508] ENSG00000204335 SP5 Sp5 transcription factor 0.048312303 [Source:HGNC Symbol;Acc:HGNC:14529] ENSG00000204241 0.04840783 ENSG00000099625 CBARP CACN beta subunit associated regulatory protein 0.048411296 [Source:HGNC Symbol;Acc:HGNC:28617] ENSG00000143450 OAZ3 ornithine decarboxylase antizyme 3 0.048617065 [Source:HGNC Symbol;Acc:HGNC:8097] ENSG00000015520 NPC1L1 NPC1 like intracellular cholesterol transporter 1 0.048746819 [Source:HGNC Symbol;Acc:HGNC:7898] ENSG00000188162 OTOG otogelin 0.048746819 [Source:HGNC Symbol;Acc:HGNC:8516] ENSG00000125492 BARHL1 BarH like homeobox 1 0.048820483 [Source:HGNC Symbol;Acc:HGNC:953] ENSG00000145832 SLC25A48 solute carrier family 25 member 48 0.048934402 [Source:HGNC Symbol;Acc:HGNC:30451] ENSG00000185686 PRAME preferentially expressed antigen in melanoma 0.048934402 [Source:HGNC Symbol;Acc:HGNC:9336] ENSG00000229147 SMPD4P2 sphingomyelin phosphodiesterase 4 pseudogene 2 0.049012128 [Source:HGNC Symbol;Acc:HGNC:39674]

A listing of selected and preferred AC3 RNA markers of impending flare, based on their scores and relevance to sublining fibroblast cells is provided below in Table 9. These markers are particularly selected for determining and predicting impending RA flares. The markers are selected from COL1A2, COL5A1, COL16A1, COL14A1, COL4A2, PXDN, ST5, DCLK1, SCARA5, EGFR, EGR1 and ZFHX4.

The markers include several genes for collagen alpha chain subunits, including COL1A2, COL5A1, COL16A1, COL14A1 and COL4A2, as follows: COL1A2 Collagen alpha-2(I) chain. This gene encodes the alpha. 2 (pro-a2(1)) chain component of type I collagen, the fibrillary collagen found in most connective tissues; COL5A1 Collagen Type V Alpha I Chain a component of type V collagen, which is a low abundance fibrillar collagen: COL16A1 Collagen alpha-1(XVI) chain. This gene encodes the alpha chain of type XVI collagen, a member of the FACIT collagen family (fibril-associated collagens with interrupted helices). Collage type XVI is a fibril-forming collagen that maintains the integrity of the extracellular-matrix: COL14A1 Collagen alpha-1(XIV) chain is a protein that in humans is encoded by the COL14A I gene. It likely plays a role in collagen binding and cell-cell adhesion: COL4A2 The COL4A2 gene encodes the alpha-2 chain of type IV collagen. Type IV collagen is associated with laminin, entactin, and heparan sulfate proteoglycans to form the sheetlike basement membranes that separate epithelium from connective tissue.

Additional markers are PXDN, ST5, DCLK1, SCARA5, EGFR, EGR1 and ZFHX4. PXDN (peroxidasin) is a heme-containing peroxidase that is secreted into the extracellular matrix and is involved in extracellular matrix formation, ST5 (Suppression Of Tumorigenicity 5 protein), also called DENN Domain Containing 23. This gene was identified by its ability to suppress the tumorigenicity of Hela cells in nude mice. The protein encoded by this gene contains a C-terminal region that shares similarity with the Rab 3 family of small GTP binding proteins. This protein preferentially binds to the SH3 domain of c-Abl kinase, and acts as a regulator of MAPK1/ERK2 kinase, which may contribute to its ability to reduce the tumorgenic phenotype in cells. May be involved in cytoskeletal organization and tumorigenicity. DCLK1 (Doublecortin Like Kinase 1) is a microtubule-associated protein kinase—a serine/threonine-protein kinase. Doublecortin Like Kinase 1 has been identified as a tuft cell marker in the small intestine and has been reported to mark tumor stem cells in the intestine and pancreas. SCARA5 (Scavenger receptor class A, member 5) is involved in lineage commitment and differentiation of mesenchymal stem cells to adipocytes. EGFR corresponds to epidermal growth factor receptor and is a cell membrane spanning protein induces cell differentiation and proliferation. Alteration and overexpression associated with various cancers. Numerous EGFR antibodies, including specific neutralizing antibodies, have been developed and are in clinical development or clinical practice for applications in cancer. EGR1 (Early growth response protein 1)—also known as ZNF268 (zinc finger protein 268) or NGFI-A (nerve growth factor-induced protein A). EGR-1 is a mammalian transcription factor. EGR-1 is a mechano-sensitive transcriptional factor that stimulates IGF-1R transcription, resulting in vascular remodeling of vein grafts. Early growth response protein 1 is a transcription factor that is rapidly induced by growth factors, cytokines, and stress signals such as radiation, injury, or mechanical stress. ZFHX4 (Zinc Finger Homeobox 4) Predicted to have RNA polymerase II proximal promoter sequence-specific DNA binding activity. RNA polymerase If specific DNA-binding transcription factor activity.

Notably all of the markers provided in Table 9 are also listed in Table 5 above, which provided transcripts common to synovial sublining fibroblasts and AC3. Table 5 also included the α collagen chain gene COL3A1, COMP, FNDC1, GALNT15, SULF1, GPX8 and IGFEP6 COL3A2 corresponds to collagen Type III alpha 1 chain. COMP (cartilage oligomeric matrix protein) Can mediate the interaction of chondrocytes with the cartilage extracellular matrix and may play a role in the structural integrity of cartilage via its interaction with other extracellular matrix proteins such as the collagens and fibronectin. FNDC1 (fibronectin Type III domain containing 1) has alternative names Activation-associated cDNA protein and expressed in synovial lining protein and is an activator of G-protein signaling. GALNT15 (Polypeptide N-Acetylgalactosaminyltransferase 15) is a membrane-bound polypeptide N-acetylgalactosaminyltransferases that catalyzes the first step in mucin-type O-glycosylation of peptides in the Golgi apparatus. SULF1 (Sulfatase 1) is an extracellular heparan sulfate endosulfatase. The enzyme is secreted through the Golgi and is subsequently localized to the cell surface and selectively removes 6-O-sulfate groups from heparan sulfate chains of heparan sulfate proteoglycans. GPX8 (Glutathione Peroxidase 8) is a protein disulfide isomerase and is involved in cellular response to oxidative stress, reducing H2O2 content and oxidative stress in the ER. IGFBP6 (Insulin-like growth factor-binding protein 6) binds insulin-like growth factor and fibronectin and has been shown to modulate the growth promoting effects of the IGFs on cell culture.

TABLE 9 RNA Markers of Impending Flare Col- pct umn PCT nonzero baseMean SYMBOL 1 geneset ENSG Gene AUC nonzero other prime COL1A2 SC- Fibroblast-CD34+ ENSG00000164692 ENSG00000164692.13 0.84468179 1 0.532809984 51.509861398 F1 sublining (SC-F1) COL1A2 SC- Fibroblast-HLA-DRAhi ENSG00000164692 ENSG00000164692.13 0.921394835 1 0.509613353 51.509861398 F2 sublining (SC-F2) COL1A2 SC- Fibroblast-DKK3+ ENSG00000164692 ENSG00000164692.13 0.906702534 1 0.555704441 51.509861398 F3 sublining (SC-F3) PXDN SC- Fibroblast-HLA-DRAhi ENSG00000130508 ENSG00000130508.6 0.843306415 0.831710709 0.16670188 24.409015138 F2 sublining (SC-F2) PXDN SC- Fibroblast-DKK3+ ENSG00000130508 ENSG00000130508.6 0.836927155 0.881578947 0.227029096 24.409015138 F3 sublining (SC-F3) COL5A1 SC- Fibroblast-CD34+ ENSG00000130635 ENSG00000130635.11 0.769189965 0.809917355 0.263486312 24.050387975 F1 sublining (SC-F1) COL5A1 SC- Fibroblast-HLA-DRAhi ENSG00000130635 ENSG00000130635.11 0.884892773 0.95132128 0.214874287 24.050387975 F2 sublining (SC-F2) COL5A1 SC- Fibroblast-DKK3+ ENSG00000130635 ENSG00000130635.11 0.917280819 0.98245614 0.282733538 24.050387975 F3 sublining (SC-F3) ZFHX4 SC- Fibroblast-CD34+ ENSG00000091656 ENSG00000091656.11 0.778380395 0.714876033 0.207125604 23.828346616 F1 sublining (SC-F1) ZFHX4 SC- Fibroblast-DKK3+ ENSG00000091656 ENSG00000091656.11 0.789767117 0.802631579 0.228177642 23.828346616 F3 sublining (SC-F3) COL16A1 SC- Fibroblast-HLA-DRAhi ENSG00000084636 ENSG00000084636.12 0.87323477 0.835883171 0.105852525 23.789446496 F2 sublining (SC-F2) ST5 SC- Fibroblast-HLA-DRAhi ENSG00000166444 ENSG00000166444.13 0.833490889 0.816411683 0.158673146 23.39530374 F2 sublining (SC-F2) DCLK1 SC- Fibroblast-CD34+ ENSG00000133083 ENSG00000133083.10 0.786731154 0.700413223 0.168075684 23.123692573 F1 sublining (SC-F1) DCLK1 SC- Fibroblast-HLA-DRAhi ENSG00000133083 ENSG00000133083.10 0.831312828 0.799721836 0.126558208 23.123692573 F2 sublining (SC-F2) EGR1 SC- Fibroblast-CD34+ ENSG00000120738 ENSG00000120738.7 0.753816991 0.950413223 0.650764895 21.499587093 F1 sublining (SC-F1) EGR1 SC- Fibroblast-HLA-DRAhi ENSG00000120738 ENSG00000120738.7 0.805075452 0.993045897 0.629410522 21.499587093 F2 sublining (SC-F2) COL14A1 SC- Fibroblast-CD34+ ENSG00000187955 ENSG00000187955.7 0.886990583 0.983471074 0.305354267 21.350721991 F1 sublining (SC-F1) COL14A1 SC- Fibroblast-HLA-DRAhi ENSG00000187955 ENSG00000187955.7 0.917607177 0.991655076 0.27044158 21.350721991 F2 sublining (SC-F2) COL14A1 SC- Fibroblast-DKK3+ ENSG00000187955 ENSG00000187955.7 0.852312874 0.969298246 0.339203675 21.350721991 F3 sublining (SC-F3) SCARA5 SC- Fibroblast-CD34+ ENSG00000168079 ENSG00000168079.12 0.749160744 0.785123967 0.289653784 20.554709341 F1 sublining (SC-F1) SCARA5 SC- Fibroblast-DKK3+ ENSG00000168079 ENSG00000168079.12 0.819901316 0.890350877 0.309341501 20.554709341 F3 sublining (SC-F3) COL4A2 SC- Fibroblast-HLA-DRAhi ENSG00000134871 ENSG00000134871.13 0.841252655 0.866481224 0.187618846 12.249482672 F2 sublining (SC-F2) EGFR SC- Fibroblast-CD34+ ENSG00000146648 ENSG00000146648.11 0.763756222 0.729338843 0.230072464 10.692550335 F1 sublining (SC-F1) EGFR SC- Fibroblast-HLA-DRAhi ENSG00000146648 ENSG00000146648.11 0.803273527 0.820584145 0.191421931 10.692550335 F2 sublining (SC-F2)

PRIME Cells

These unusual RNAs identified in blood as indicators of an RA flare, particularly those of AC3, identified a unique cell in blood samples denoted Pre-Inflammatory Mesenchymal Cells (PRIME cells). RNA sequencing of these cells confirmed that they were enriched with AC3 cluster genes, synovial fibroblast genes, and expressed classic synovial fibroblast genes such as FAP, DKK3, CDH11 as well as collagens and laminins. PRIME cells are activated just prior to flare and are then evident at flare in inflamed synovium as inflammatory sublining fibroblasts.

Cell surface markers characteristic of the PRIME cells identified and described herein are PDPN+, CD45− and CD31−. PRIME cells can be sorted or characterized as CD45−, CD31−PDPN+ cells. Also, the cell surface receptor and marker IL17RD+ can additionally be utilized to differentiate, identify and characterize PRIME cells. IL17RD is an AC3 gene marker (see Table 3 above). CD45 and CD31 are often present on cells in blood, therefore a blood cell which lacks both of these specific markers would be unusual. CD45 is a pan-leukocyte protein with tyrosine phosphatase activity involved in the regulation of signal transduction in hematopoiesis. CD45 is also known as protein tyrosine phosphatase, receptor type, C (PTPRC). CD45 was originally designated leukocyte common antigen, reflecting its general expression on leukocytes. CD31 represents platelet endothelial cell adhesion molecule (PECAM-1). This molecule plays a key role in removing aged neutrophils from the body, and is found on the surface of platelets, monocytes, neutrophils and some types of T cells.

In contrast, the presence of PDPN—and also of IL17RD—on the surface of a population of cells, particularly CD45− and CD31− cells in blood, is unusual. PDPN (Podaplanin) is a well conserved mucin-type transmembrane protein and is heavily O-glycosylated with diverse distribution in human tissues. Podaplanin binds to C-type lectin receptor-2 (CLEC-2) and is associated with malignant progression and tumor metastasis in several types of cancer. Anti-podaplanin antibody has been evaluated and shown effective in LPS-induced lung injury (Lax S et al (2017) BMJ Open Respiratory Res 4:e000257.doi:10.11361/bmjresp-2017-000257). Podaplanin antibodies have been investigated in pulmonary metastasis and in malignant mesothelioma (Kato Y (2015) Oncotarget 6(34):36003-36018; Abe S et al (2013) J Immunol 190(12):6239-6249).

IL17RD (IL-17 Receptor D), a membrane protein of the IL-17 receptor family, is a feedback loop inhibitor of fibroblast growth factor mediated Ras-MAPK signaling and ERK activation. IL17RD binds IL-17A and mediates pro-inflammatory gene expression downstream of IL-17A.

Antibodies targeting IL-17 cytokines and their receptors are being used in treatment of some autoimmune diseases. In RA, IL-17A acts locally on synoviocytes and osteoblasts contributing to synovitis and joint disruption, Although some positive results have been seen in psoriasis and psoriatic arthritis, results with biologics targeting IL-17 in RA have been mixed, underscoring the need to identify patients or clinical/biological scenarios where therapeutics such as IL-17 biologics will be effective (Robert M and Miossec P (2019) Front Med 5:364; doi:10.3389/fmed.2018.00364; Fragoulis G E et al (2016) Ann Rev Med 67:337-353). Targeting IL-17 or IL17D based on RNA markers and/or PRIME cell analysis may be a more effective approach to treatment of RA, particularly if administration upon recognition of an imminent flare could be implemented.

This invention may be embodied in other forms or carried out in other ways without departing from the spirit or essential characteristics thereof. The present disclosure is therefore to be considered as in all aspects illustrated and not restrictive, the scope of the invention being indicated by the appended Claims, and all changes which come within the meaning and range of equivalency are intended to be embraced therein.

Various references are cited throughout this Specification, each of which is incorporated herein by reference in its entirety. 

1. A method for monitoring and predicting a rheumatoid arthritis (RA) flare or increased RA disease activity in a patient comprising: (a) isolating a blood sample from said patient; (b) evaluating the blood sample for expression or quantitatively increased amounts of one or more sets of antecedent RNA markers, protein markers or cell markers selected from: (i) markers or proteins selected from COL1A2, COL5A1, COL16A1, COL14A1, COL4A2, PXDN, ST5, DCLK1, SCARA5, EGFR, EGR1, ZFHX4, COL3A1, COMP, FNDC1, GALNT15, SULF1, GPX8 and IGFBP6 as set out in Table 5; (ii) markers or proteins selected from COL1A2, COL5A1, COL16A1, COL14A1, COL4A2, PXDN, ST5, DCLK1, SCARA5, EGFR, EGR1 and ZFHX4 as set out in Table 9; (iii) AC2 markers or proteins as provided in Table 7; (iv) AC3 markers or proteins as provided in Table 8; and (v) cell markers CD45− CD31−PDPN+; (c) wherein the expression or quantitatively increased amounts of the RNA markers or proteins or the presence of the cell markers predicts an impending RA flare.
 2. The method of claim 1, wherein the expression or quantitatively increased amounts of the AC2 RNA markers or proteins predicts an RA flare in about 2 weeks or about 12-14 days or up to 3 weeks.
 3. The method of claim 1, wherein the expression or quantitatively increased amounts of the AC3 RNA markers or proteins predicts an RA flare in about 1 week or about 5-7 days or up to 2 weeks.
 4. (canceled)
 5. (canceled)
 6. The method of claim 1, wherein a subset of at least 10 of the AC2 or AC3 markers are evaluated.
 7. The method of claim 1, wherein a subset of at least 10 of the AC2 and at least 10 of the AC3 markers are evaluated.
 8. The method of claim 1, wherein sublining fibroblast markers selected from the AC3 markers or proteins are evaluated.
 9. The method of claim 1, wherein AC3 markers or proteins expressed by CD34+, HLADR+ and DKK3+ cells are evaluated.
 10. The method of claim 1, wherein the cell marker IL17RD is also evaluated.
 11. The method of claim 1, wherein RNA expression is assessed by RT PCR.
 12. The method of claim 1 wherein protein expression is assessed using specific antibodies.
 13. The method of claim 1 wherein cell markers are evaluated using FACs analysis.
 14. The method of claim 1 wherein the antecedent RNA markers or protein markers or selected from: (a) markers or proteins selected from COL1A2, COL5A1, COL16A1, COL14A1, COL4A2, PXDN, ST5, DCLK1, SCARA5, EGFR, EGR1, ZFHX4, COL3A1, COMP, FNDC1, GALNT15, SULF1, GPX8 and IGFBP6 as set out in Table 5; (b) markers or proteins selected from COL1A2, COL5A1, COL16A1, COL14A1, COL4A2, PXDN, ST5, DCLK1, SCARA5, EGFR, EGR1 and ZFHX4 as set out in Table 9; and (c) AC3 markers or proteins as provided in Table 8; are reduced, significantly decreased, nearly absent, or absent in peripheral blood during an RA flare or once a patient exhibits symptoms of an RA flare.
 15. A method for predicting an impending RA flare and treating a flare in a patient, the method comprising: a) isolating a blood sample from the patient; b) contacting the blood sample with reagents specific for markers selected from a panel of RNA or protein markers to assess expression of the RNA or protein markers, wherein the panel of RNA or protein markers is selected from: (i) markers or proteins selected from COL1A2, COL5A1, COL16A1, COL14A1, COL4A2, PXDN, ST5, DCLK1, SCARA5, EGFR, EGR1, ZFHX4, COL3A1, COMP, FNDC1, GALNT15, SULF1, GPX8 and IGFBP6 as set out in Table 5; (ii) markers or proteins selected from COL1A2, COL5A1, COL16A1, COL14A1, COL4A2, PXDN, ST5, DCLK1, SCARA5, EGFR, EGR1 and ZFHX4 as set out in Table 9; (iii) AC2 markers or proteins as provided in Table 7; and (iv) AC3 markers or proteins as provided in Table 8; c) comparing expression of the markers selected from a panel of RNA or protein markers in the blood sample to expression of the markers in a control blood sample to determine if expression of the markers selected from a panel of RNA or protein markers in the blood sample is increased relative to expression in the control blood sample, wherein detection of increased expression serves to predict an impending RA flare in a patient; and treating the patient thereby diagnosed with an impending RA flare by administering a therapeutically effective amount of one or more disease modifying agent for treating RA.
 16. The method of claim 15, wherein RNA expression is assessed by RT PCR.
 17. The method of claim 15, wherein protein expression is assessed using specific antibodies.
 18. The method of claim 15, wherein the expression or quantitatively increased amounts of the AC2 RNA markers or proteins predicts an RA flare in about 2 weeks or about 12-14 days or about 3 weeks.
 19. The method of claim 15, wherein the expression or quantitatively increased amounts of RNA or protein markers selected from: (a) markers or proteins selected from COL1A2, COL5A1, COL16A1, COL14A1, COL4A2, PXDN, ST5, DCLK1, SCARA5, EGFR, EGR1, ZFHX4, COL3A1, COMP, FNDC1, GALNT15, SULF1, GPX8 and IGFBP6; (b) markers or proteins selected from COL1A2, COL5A1, COL16A1, COL14A1, COL4A2, PXDN, ST5, DCLK1, SCARA5, EGFR, EGR1 and ZFHX4; and (c) the AC3 RNA markers or proteins; predicts an RA flare in about 1 week or about 5-7 days or about 2 weeks.
 20. The method of claim 15, wherein the disease modifying agent for treating RA is one or more agent selected from a nonsteroidal anti-inflammatory drug (NSAID), steroid, methotrexate, disease-modifying antirheumatic drug (DMARDs), biologic DMARD, and oral janus kinase (JAK) inhibitor.
 21. The method of claim 20, wherein the DMARD is selected from methotrexate (Trexall, Otrexup), leflunomide (Arava), hydroxychloroquine (Plaquenil) and sulfasalazine (Azulfidine).
 22. The method of claim 20, wherein the biologic DMARD is selected from abatacept (Orencia), adalimumab (Humira), anakinra (Kineret), baricitinib (Olumiant), certolizumab (Cimzia), etanercept (Enbrel), golimumab (Simponi), infliximab (Remicade), rituximab (Rituxan), sarilumab (Kevzara), tocilizumab (Actemra) and tofacitinib (Xeljanz).
 23. The method of claim 20, wherein the biologic DMARD is a tumor necrosis factor (TNF) inhibitor.
 24. The method of claim 20, wherein the biologic DMARD is combined with an NSAID and/or with methotrexate.
 25. The method of claim 20, wherein the JAK inhibitor is selected from tofacitinib (Xeljanz and Xeljanz XR), baricitinib (Olumiant), and upadacitinib (Rinvoq).
 26. The method of claim 15, wherein the disease modifying agent for treating RA is an IL-17 antibody or an IL17RD blocking antibody.
 27. A circulating pre-inflammatory mesenchymal (PRIME) cell characterized as a CD45−CD31−PDPN+ cell, wherein the presence of the cell in peripheral blood is indicative or predictive of an impending RA flare.
 28. The PRIME cell of claim 27, which additionally expresses IL17RD and is IL17RD+.
 29. A method of predicting an impending RA flare comprising evaluating a blood sample from a patient for the presence of a PRIME cell of claim 27, wherein the presence of detectable PRIME cells in peripheral blood in a patient predicts an impending RA flare in the patient.
 30. The method of claim 29, further evaluating for the presence of IL17RD on a CD45−CD31−PDPN+ cell.
 31. A method for evaluating and treating an impending flare in an RA patient comprising evaluating the peripheral blood of a patient for the presence of a PRIME cell of claim 27 which additionally expresses IL17RD and is IL17RD+ and treating a patient that is positive for PRIME cells in their peripheral blood with a disease modifying agent for RA.
 32. The method of claim 31, wherein the patient is treated with an IL-17 or IL-17RD antibody.
 33. The method of claim 32, wherein the patient is further treated with an anti-inflammatory agent and/or an immune modulating agent.
 34. A set of RNA or protein markers for evaluating and predicting an impending RA flare in a patient comprising the markers selected from: (i) markers selected from COL1A2, COL5A1, COL16A1, COL14A1, COL4A2, PXDN, ST5, DCLK1, SCARA5, EGFR, EGR1, ZFHX4, COL3A1, COMP, FNDC1, GALNT15, SULF1, GPX8 and IGFBP6 as set out in Table 5; (ii) markers selected from COL1A2, COL5A1, COL16A1, COL14A1, COL4A2, PXDN, ST5, DCLK1, SCARA5, EGFR, EGR1 and ZFHX4 as set out in Table 9; (iii) a subset of at least 20 markers from the AC2 markers provided in Table 7; and (iv) a subset of at least 20 markers from the AC3 markers provided in Table
 8. 35. The marker set of claim 34, wherein the subset of AC2 markers comprises naïve B cell gene markers and markers of developmental pathways for naïve B cells and leukocytes.
 36. The marker set of claim 34, wherein the subset of AC3 markers comprises markers of cartilage morphogenesis, endochondral bone growth, extracellular matrix organization and sublining fibroblasts.
 37. A system or kit for predicting an impending RA flare comprising a set of markers of claim 34 or a set of probes and/or antibodies for evaluating a set of markers of claim
 34. 38. The system or kit of claim 37, which further comprises a means for collection of the patient's blood by fingerstick. 